Pimozide: Difference between revisions

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	{{pp-pc1}}		{{pp-pc1}}
			{{Use dmy dates\|date=November 2017}}
			{{Use American English\|date=November 2017}}

	{{drugbox		{{drugbox
	\| Watchedfields = changed		\| Watchedfields = changed
	\| verifiedrevid = 464206733		\| verifiedrevid = 464206733
	\| IUPAC_name = 1--4-piperidinyl]-1,3-dihydro-2''H''-benzimidazole-2-one		\| IUPAC_name = 1--4-piperidinyl]-1,3-dihydro-2''H''-benzimidazole-2-one
	\| image = Pimozide.svg		\| image = Pimozide.svg
	\| width = 200		\| width = 200

	<!--Clinical data-->		<!--Clinical data-->
	\| tradename = Orap		\| tradename = Orap
	\| Drugs.com = {{drugs.com\|monograph\|pimozide}}		\| Drugs.com = {{drugs.com\|monograph\|pimozide}}
	\| MedlinePlus = a686018		\| MedlinePlus = a686018
	\| licence_US = Pimozide		\| licence_US = Pimozide
	\| pregnancy_AU = B1		\| pregnancy_AU = B1
	\| pregnancy_US = C		\| pregnancy_US = C
	\| legal_AU = S4		\| legal_AU = S4
	\| legal_US = Rx-only		\| legal_US = Rx-only
	\| routes_of_administration = Oral		\| routes_of_administration = Oral

	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	\| bioavailability = 40-50%		\| bioavailability = 40-50%
	\| metabolism = ], ] and ]		\| metabolism = ], ] and ]
	\| elimination_half-life = 55 hours (adults), 66 hours (children)		\| elimination_half-life = 55 hours (adults), 66 hours (children)
	\| excretion = Urine		\| excretion = Urine

	<!--Identifiers-->		<!--Identifiers-->
	\| CAS_number_Ref = {{cascite\|correct\|??}}		\| CAS_number_Ref = {{cascite\|correct\|??}}
	\| CAS_number = 2062-78-4		\| CAS_number = 2062-78-4
	\| ATC_prefix = N05		\| ATC_prefix = N05
	\| ATC_suffix = AG02		\| ATC_suffix = AG02
	\| PubChem = 16362		\| PubChem = 16362
	\| IUPHAR_ligand = 90		\| IUPHAR_ligand = 90
	\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}		\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}
	\| DrugBank = DB01100		\| DrugBank = DB01100
	\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}		\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
	\| ChemSpiderID = 15520		\| ChemSpiderID = 15520
	\| UNII_Ref = {{fdacite\|correct\|FDA}}		\| UNII_Ref = {{fdacite\|correct\|FDA}}
	\| UNII = 1HIZ4DL86F		\| UNII = 1HIZ4DL86F
	\| KEGG_Ref = {{keggcite\|correct\|kegg}}		\| KEGG_Ref = {{keggcite\|correct\|kegg}}
	\| KEGG = D00560		\| KEGG = D00560
	\| ChEBI_Ref = {{ebicite\|correct\|EBI}}		\| ChEBI_Ref = {{ebicite\|correct\|EBI}}
	\| ChEBI = 8212		\| ChEBI = 8212
	\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}		\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}
	\| ChEMBL = 1423		\| ChEMBL = 1423

	<!--Chemical data-->		<!--Chemical data-->
	\| C=28 \| H=29 \| F=2 \| N=3 \| O=1		\|C=28 \|H=29 \|F=2 \|N=3 \|O=1
	\| molecular_weight = 461.56 g/mol		\| molecular_weight = 461.56 g/mol
	\| smiles = Fc1ccc(cc1)C(c2ccc(F)cc2)CCCN5CCC(N4c3ccccc3NC4=O)CC5		\| smiles = Fc1ccc(cc1)C(c2ccc(F)cc2)CCCN5CCC(N4c3ccccc3NC4=O)CC5
	\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}		\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChI = 1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34)		\| StdInChI = 1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34)
	\| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}}		\| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChIKey = YVUQSNJEYSNKRX-UHFFFAOYSA-N		\| StdInChIKey = YVUQSNJEYSNKRX-UHFFFAOYSA-N
	}}		}}

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	== Medical uses ==		== Medical uses ==

	Pimozide is used in its oral preparation in ] and chronic ] (on-label indications in Europe only), Tourette syndrome and resistant ] (Europe, USA and Canada).		Pimozide is used in its oral preparation in ] and chronic ] (on-label indications in Europe only), Tourette syndrome and resistant ] (Europe, USA and Canada).

	Pimozide has been used in the treatment of ] and ].<ref>Munro, A. (1999)''Delusional disorder''. Cambridge: Cambridge University Press. {{ISBN\|0-521-58180-X}}.</ref> It has also been used for ].<ref name="pmid12639456">{{cite journal \|author=van Vloten WA \|title=Pimozide: use in dermatology \|journal=Dermatol. Online J. \|volume=9 \|issue=2 \|pages=3 \|date=March 2003 \|pmid=12639456 \|doi=\|url=http://dermatology.cdlib.org/92/reviews/pimozide/vanvloten.html }}</ref>		Pimozide has been used in the treatment of ] and ].<ref>Munro, A. (1999)''Delusional disorder''. Cambridge: Cambridge University Press. {{ISBN\|0-521-58180-X}}.</ref> It has also been used for ].<ref name="pmid12639456">{{cite journal \|author = van Vloten WA \|title = Pimozide: use in dermatology \|journal = Dermatol. Online J. \|volume = 9 \|issue = 2 \|pages = 3 \|date = March 2003 \|pmid = 12639456 \|doi = \|url = http://dermatology.cdlib.org/92/reviews/pimozide/vanvloten.html }}</ref>

	Use as an antibiotic for '']'' has been described.<ref name="pmid19015342">{{cite journal \|vauthors=Lieberman LA, Higgins DE \|title=A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection\|journal=Antimicrob. Agents Chemother. \|volume=53 \|issue=2 \|pages=756–64 \|date=February 2009 \|pmid=19015342 \|pmc=2630664\|doi=10.1128/AAC.00607-08 \|url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=19015342}}</ref>		Use as an antibiotic for '']'' has been described.<ref name="pmid19015342">{{cite journal \|vauthors = Lieberman LA, Higgins DE \|title = A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection \|journal = Antimicrob. Agents Chemother. \|volume = 53 \|issue = 2 \|pages = 756–64 \|date = February 2009 \|pmid = 19015342 \|pmc = 2630664 \|doi = 10.1128/AAC.00607-08 \|url = http://aac.asm.org/cgi/pmidlookup?view=long&pmid=19015342 }}</ref>

	It has also been used once in the treatment of ], although whether the patient has since experienced remission is unknown. And it is recommended to be considered in cases of "doubtful gender dysphoria".<ref>{{cite journal\|title=Pharmacotherapy with pimozide should be considered in cases of doubtful gender dysphoria.\|date=June 1996\|journal=Australian & New Zealand Journal of Psychiatry\|author=B. K. Puri, MA, MB, BChir. MRCPsychResearch Fellow, I. Singh, MBBS. FRCPsych\|pmid=8839957\|doi=10.3109/00048679609065010\|volume=30\|issue=3\|page=422-425\|url=http://journals.sagepub.com/doi/abs/10.3109/00048679609065010}}</ref>		It has also been used once in the treatment of ], although whether the patient has since experienced remission is unknown. And it is recommended to be considered in cases of "doubtful gender dysphoria".<ref>{{cite journal \|title = Pharmacotherapy with pimozide should be considered in cases of doubtful gender dysphoria. \|date = June 1996 \|journal = Australian & New Zealand Journal of Psychiatry \|author = B. K. Puri, MA, MB, BChir. MRCPsychResearch Fellow, I. Singh, MBBS. FRCPsych \|pmid = 8839957 \|doi = 10.3109/00048679609065010 \|volume = 30 \|issue = 3 \|page = 422-425 \|url = http://journals.sagepub.com/doi/abs/10.3109/00048679609065010 }}</ref>

	== Side effects ==		== Side effects ==

	Very common (>10% frequency) side effects include:<ref name = MSR/><ref name = EMC/><ref name = MD/><ref name = DM/>		Very common (>10% frequency) side effects include:<ref name = MSR /><ref name = EMC /><ref name = MD /><ref name = DM />

	* ]		* ]
	* Constipation		* Constipation
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	* Dry mouth		* Dry mouth
	* ]		* ]
	* Nocturia		* ]
	* Somnolence		* ]
	* Speech disorder		* Speech disorder

	===Contraindications===		=== Contraindications ===

	It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation.<ref name = EMC/> Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or ].<ref name = EMC/> Likewise its use is also advised against in individuals with uncorrected ] and ] or clinical significant cardiac disorders (e.g. a recent ] or ].<ref name =EMC/> It is also contraindicated in individuals being cotreated with ] or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives.<ref name = EMC/> Likewise its use is contraindicated in individuals receiving treatment with ], ], or ] inhibitors.<ref name = EMC/>		It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation.<ref name = EMC /> Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or ].<ref name = EMC /> Likewise its use is also advised against in individuals with uncorrected ] and ] or clinical significant cardiac disorders (e.g. a recent ] or ].<ref name =EMC /> It is also contraindicated in individuals being cotreated with ] or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives.<ref name = EMC /> Likewise its use is contraindicated in individuals receiving treatment with ], ], or ] inhibitors.<ref name = EMC />

			=== Overdose ===

		⚫	Pimozide overdose presents with severe ], ], ], QT interval prolongation and ventricular arrhythmias including ].<ref name = EMC /> Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose.<ref name = EMC /> Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.<ref name = EMC />

	==~~=Overdose=~~==		== Efficacy ==
⚫	Pimozide overdose presents with severe ], ], ], QT interval prolongation and ventricular arrhythmias including ].<ref name = EMC/> Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose.<ref name = EMC/> Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.<ref name = EMC/>

		⚫	A 2013 ] compared pimozide with other antipsychotics for schizophrenia or related psychoses:
	==Efficacy==
⚫	A 2013 ] compared pimozide with other antipsychotics for schizophrenia or related psychoses:
	{\| class="wikitable"		{\| class="wikitable"
	\|+ Pimozide versus any other antipsychotic<ref name=Mot2013>{{cite journal\|last1=Mothi\| first1=M\| last2=Sampson\|first2=S\| first3=\| last3=\|title=Pimozide for schizophrenia or related psychoses\|journal=Cochrane Database of Systematic Reviews\|date=2013\|volume=11\|url=http://www.cochrane.org/CD001949/SCHIZ_pimozide-for-schizophrenia-or-related-psychoses\|pages=CD001949.pub3 \|DOI=10.1002/14651858.CD001949.pub3}}</ref>		\|+ Pimozide versus any other antipsychotic<ref name=Mot2013>{{cite journal \|last1 = Mothi \|first1 = M \|last2 = Sampson \|first2 = S \|first3 = \|last3 = \|title = Pimozide for schizophrenia or related psychoses \|journal = Cochrane Database of Systematic Reviews \|date = 2013 \|volume = 11 \|url = http://www.cochrane.org/CD001949/SCHIZ_pimozide-for-schizophrenia-or-related-psychoses \|pages = CD001949.pub3 \|DOI=10.1002/14651858.CD001949.pub3 }}</ref>
	\|-		\|-
	! Summary		! Summary
	\|-		\|-
	\|Enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with ] similar to that of other, more commonly used ] drugs such as chlorpromazine for people with schizophrenia.<ref name=Mot2013/>		\|Enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with ] similar to that of other, more commonly used ] drugs such as chlorpromazine for people with schizophrenia.<ref name=Mot2013 />
	\|-		\|-
	\| style="padding:0;" \|		\| style="padding:0;" \|
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	! colspan="4" style="text-align: left;"\| Global state		! colspan="4" style="text-align: left;"\| Global state
	\|-		\|-
	\| Relapse<br>Follow-up: average 38 weeks \|\| These is no clear difference between pimozide and other antipsychotic drugs. Data supporting this finding are based on moderate quality evidence.		\| Relapse<br />Follow-up: average 38 weeks \|\| These is no clear difference between pimozide and other antipsychotic drugs. Data supporting this finding are based on moderate quality evidence.
	\|\| ] 0.82 (0.57 to 1.17) \|\| ]		\|\| ] 0.82 (0.57 to 1.17) \|\| ]
	\|-		\|-
	! colspan="4" style="text-align: left;"\| ]		! colspan="4" style="text-align: left;"\| ]
	\|-		\|-
	\| No improvement<br>Follow-up: 16 weeks \|\| There is not a clear difference between pimozide and other antipsychotic drugs for this mental state outcome but data supporting this finding are very limited.		\| No improvement<br />Follow-up: 16 weeks \|\| There is not a clear difference between pimozide and other antipsychotic drugs for this mental state outcome but data supporting this finding are very limited.
	\|\| ] 1.09 (0.08 to 15.41) \|\| ]		\|\| ] 1.09 (0.08 to 15.41) \|\| ]
	\|-		\|-
	\| Presence of first-rank symptoms<br>Follow-up: 3-12 months\|\| Pimozide may reduce the chance of experiencing these problematic symptoms but there is no clear difference between people given pimozide and those receiving any other antipsychotic. These findings are based on data of low quality.		\| Presence of first-rank symptoms<br />Follow-up: 3-12 months\|\| Pimozide may reduce the chance of experiencing these problematic symptoms but there is no clear difference between people given pimozide and those receiving any other antipsychotic. These findings are based on data of low quality.
	\|\| ] 0.53 (0.25 to 1.11) \|\| ]		\|\| ] 0.53 (0.25 to 1.11) \|\| ]
	\|-		\|-
	! colspan="4" style="text-align: left;"\| ] - ] adverse effects		! colspan="4" style="text-align: left;"\| ] – ] adverse effects
	\|-		\|-
	\| Parkinsonism (rigidity)<br>Follow-up: mean 14 weeks \|\| In the short term these is no clear difference between pimozide and other antipsychotic drugs for this adverse effect. These findings are based on data of low quality. There are no data in the longer term.		\| Parkinsonism (rigidity)<br />Follow-up: mean 14 weeks \|\| In the short term these is no clear difference between pimozide and other antipsychotic drugs for this adverse effect. These findings are based on data of low quality. There are no data in the longer term.
	\|\| ] 1.25 (0.37 to 4.17) \|\| ]		\|\| ] 1.25 (0.37 to 4.17) \|\| ]
	\|-		\|-
	\| Parkinsonism (tremor)<br>Follow-up: mean 29 weeks \|\| There is no clear difference between pimozide and other antipsychotic drugs for the adverse effect of causing tremor but these findings are based on data of low quality.		\| Parkinsonism (tremor)<br />Follow-up: mean 29 weeks \|\| There is no clear difference between pimozide and other antipsychotic drugs for the adverse effect of causing tremor but these findings are based on data of low quality.
	\|\| ] 1.45 (0.68 to 3.09) \|\| ]		\|\| ] 1.45 (0.68 to 3.09) \|\| ]
	\|-		\|-
	! colspan="4" style="text-align: left;"\| Missing outcomes		! colspan="4" style="text-align: left;"\| Missing outcomes
	\|-		\|-
	\| \|\| The outcome of ] was not measured/reported in the included studies. \|\| \|\|		\| \|\| The outcome of ] was not measured/reported in the included studies. \|\| \|\|
	\|-		\|-
	\|}		\|}
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	== Pharmacology ==		== Pharmacology ==
⚫	Pimozide acts as an ] of the ], ], and ]s and the ]. It is also a ] ].

		⚫	Pimozide acts as an ] of the ], ], and ] and the ]. It is also a ] ].
⚫	Similarly to other typical antipsychotics pimozide has a high affinity for the ] and this likely results in its sexual (due to ]) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of ].<ref name="Maudsley">{{cite book \| isbn = 978-0-470-97948-8 \| title = The Maudsley prescribing guidelines in psychiatry \| last1 = Taylor \| first1 = D \|author2=Paton, C; Shitij, K \| year = 2012 \| publisher = Wiley-Blackwell \| location = West Sussex \| pages = }}</ref>

		⚫	Similarly to other typical antipsychotics pimozide has a high affinity for the ] and this likely results in its sexual (due to ]) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of ].<ref name="Maudsley">{{cite book \|isbn = 978-0-470-97948-8 \|title = The Maudsley prescribing guidelines in psychiatry \|last1 = Taylor \|first1 = D \|author2 = Paton, C; Shitij, K \|year = 2012 \|publisher = Wiley-Blackwell \|location = West Sussex \|pages = }}</ref>
⚫	{\| class = "wikitable sortable"

		⚫	{\| class="wikitable sortable"
	\|+ <big>Binding profile</big><ref group = Note>A lower K<sub>i</sub> value indicates a stronger binding</ref>		\|+ <big>Binding profile</big><ref group = Note>A lower K<sub>i</sub> value indicates a stronger binding</ref>
	! Protein !! K<sub>i</sub> (nM)<ref>{{cite web \| title = PDSP K<sub>i</sub> Database \| work = Psychoactive Drug Screening Program (PDSP)\|author1=Roth, BL \|author2=Driscol, J \| url = http://pdsp.med.unc.edu/pdsp.php \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| accessdate = 4 December 2013 \| date = 12 January 2011}}</ref> !! Notes		! Protein !! K<sub>i</sub> (nM)<ref>{{cite web \|title = PDSP K<sub>i</sub> Database \|work = Psychoactive Drug Screening Program (PDSP) \|author1 = Roth, BL \|author2 = Driscol, J \|url = http://pdsp.med.unc.edu/pdsp.php \|publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \|accessdate = 4 December 2013 \|date = 12 January 2011 }}</ref> !! Notes
	\|-		\|-
	\| ] \|\| 650 \|\|		\| ] \|\| 650 \|\|
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	\| ] \|\| 2,112 \|\|		\| ] \|\| 2,112 \|\|
	\|-		\|-
	\| ] \|\| 71 \|\|		\| ] \|\| 71 \|\|
	\|-		\|-
	\| ] \|\| 0.5 \|\| Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.<ref>{{cite journal\|title=Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression\|journal=Indian Journal of Pharmaceutical Education and Research\|volume=45\|issue=1\|pages=46–53\|date=January–March 2011\|url=http://www.ijperonline.com/jan_mar_2011/49-56.pdf\|format=PDF}}</ref>		\| ] \|\| 0.5 \|\| Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.<ref>{{cite journal \|title = Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression \|journal = Indian Journal of Pharmaceutical Education and Research \|volume = 45 \|issue = 1 \|pages = 46–53 \|date = January–March 2011 \|url = http://www.ijperonline.com/jan_mar_2011/49-56.pdf \|format = PDF }}</ref>
	\|-		\|-
	\| ] \|\| 197.7 \|\| Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension.<ref name = Maudsley/>		\| ] \|\| 197.7 \|\| Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension.<ref name = Maudsley />
	\|-		\|-
	\| ] \|\| 1,593 \|\|		\| ] \|\| 1,593 \|\|
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	\| ] \|\| 376.5 \|\|		\| ] \|\| 376.5 \|\|
	\|-		\|-
	\| ] \|\| 1,955 \|\| This receptor is believed to be responsible for the interference with glucose ] seen with some of the ] such as ] and ].<ref name="GG">{{cite book \| isbn = 978-0-07-162442-8 \| title = ] \| edition = 12th \|author1=Brunton, L \|author2=Chabner, B \|author3=Knollman, B \| year = 2010 \| publisher = McGraw-Hill Professional \| location = New York }}</ref> Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis.		\| ] \|\| 1,955 \|\| This receptor is believed to be responsible for the interference with glucose ] seen with some of the ] such as ] and ].<ref name="GG">{{cite book \|isbn = 978-0-07-162442-8 \|title = ] \|edition = 12th \|author1 = Brunton, L \|author2 = Chabner, B \|author3 = Knollman, B \|year = 2010 \|publisher = McGraw-Hill Professional \|location = New York }}</ref> Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis.
	\|-		\|-
	\| ] \|\| >10,000 \|\|		\| ] \|\| >10,000 \|\|
	\|-		\|-
	\| ] \|\| 0.33 \|\| Likely the receptor responsible for the therapeutic effects against the positive symptoms of schizophrenia of antipsychotics like pimozide as well as the prolactin-elevating and extrapyramidal side effect-generating effects of typical antipsychotics like pimozide.<ref name = GG/>		\| ] \|\| 0.33 \|\| Likely the receptor responsible for the therapeutic effects against the positive symptoms of schizophrenia of antipsychotics like pimozide as well as the prolactin-elevating and extrapyramidal side effect-generating effects of typical antipsychotics like pimozide.<ref name = GG />
	\|-		\|-
	\| ] \|\| 0.25 \|\|		\| ] \|\| 0.25 \|\|
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	\| ] \|\| 1.8 \|\|		\| ] \|\| 1.8 \|\|
	\|-		\|-
	\| ] \|\| 18 \|\| May be responsible for pimozide's high liability for prolonging the QT interval.<ref name = GG/>		\| ] \|\| 18 \|\| May be responsible for pimozide's high liability for prolonging the QT interval.<ref name = GG />
	\|-		\|-
	\| ] \|\| 692 \|\| Likely responsible for why pimozide tends to produce so little sedation.<ref name =" GG"/>		\| ] \|\| 692 \|\| Likely responsible for why pimozide tends to produce so little sedation.<ref name =" GG" />
	\|-		\|-
	\| ] \|\| 508 \|\|		\| ] \|\| 508 \|\|
	\|}		\|}

	{\| class="wikitable" align = "left"		{\| class="wikitable" align="left"
	\|+ <big>Pharmacokinetic data</big><ref name = MSR>{{cite web\|title=Oral (pimozide) dosing, indications, interactions, adverse effects, and more\|work=Medscape Reference\|publisher=WebMD\|accessdate=4 December 2013\|url=http://reference.medscape.com/drug/orap-pimozide-342982#showall}}</ref><ref name=EMC>{{cite web\|title=Oral 4 mg tablets. - Summary of Product Characteristics \|work=electronic Medicines Compendium \|publisher=Janssen-Cilag Ltd \|date=2 April 2013 \|accessdate=4 December 2013 \|url=http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ \|deadurl=yes \|archiveurl=https://web.archive.org/web/20160303230421/http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ \|archivedate=~~March~~ 3, 2016 }}</ref><ref name = MD>{{cite book\|title=Pimozide\|author=Brayfield, A\|work=Martindale: The Complete Drug Reference\|publisher=Pharmaceutical Press\|location=London, UK\|url=http://www.medicinescomplete.com.elibrary.jcu.edu.au/mc/martindale/current/7087-n.htm\|accessdate=4 December 2013\|date=12 February 2013}}</ref><ref name = DM>{{cite web\|title=ORAP (pimozide) tablet \|work=DailyMed\|publisher=Teva Select Brands\|date=July 2012\|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd9729c3-545f-4d34-9bc7-72b61e028fc4\|accessdate=4 December 2013}}</ref>		\|+ <big>Pharmacokinetic data</big><ref name = MSR>{{cite web \|title = Oral (pimozide) dosing, indications, interactions, adverse effects, and more \|work = Medscape Reference \|publisher = WebMD \|accessdate = 4 December 2013 \|url = http://reference.medscape.com/drug/orap-pimozide-342982#showall }}</ref><ref name=EMC>{{cite web \|title = Oral 4 mg tablets. - Summary of Product Characteristics \|work = electronic Medicines Compendium \|publisher = Janssen-Cilag Ltd \|date = 2 April 2013 \|accessdate = 4 December 2013 \|url = http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ \|deadurl = yes \|archiveurl = https://web.archive.org/web/20160303230421/http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ \|archivedate = 3 March 2016 }}</ref><ref name = MD>{{cite book \|title = Pimozide \|author = Brayfield, A \|work = Martindale: The Complete Drug Reference \|publisher = Pharmaceutical Press \|location = London, UK \|url = http://www.medicinescomplete.com.elibrary.jcu.edu.au/mc/martindale/current/7087-n.htm \|accessdate = 4 December 2013 \|date = 12 February 2013 }}</ref><ref name = DM>{{cite web \|title = ORAP (pimozide) tablet \|work = DailyMed \|publisher = Teva Select Brands \|date = July 2012 \|url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd9729c3-545f-4d34-9bc7-72b61e028fc4 \|accessdate = 4 December 2013 }}</ref>
	! Pharmacokinetic parameter !! Value		! Pharmacokinetic parameter !! Value
	\|-		\|-
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	==Orphan Drug 1985==		== Orphan Drug 1985 ==

	In 1985 the ] pimozide (brand name Orap) was approved by the U.S. ] (FDA or USFDA) for marketing in the U.S. for the treatment of ] (TS)<ref name="Pimozide_1985">{{cite journal \|journal=Drug Intell Clin Pharm \|date= June 1985 \|volume=19 \|number=6 \|pages=421–4 \|title=Pimozide: use in Tourette's syndrome \|author1=Colvin CL \|author2=Tankanow RM \|pmid=3891283 }}</ref> — one of a number of rare diseases — which also included ], ], ], and ] — in the United States ], a law enacted to facilitate development of orphan drugs for conditions which affect small numbers of individuals residing in the United States.<ref name="GPO">{{cite web \| url=http://www.gpo.gov/fdsys/pkg/STATUTE-96/pdf/STATUTE-96-Pg2049.pdf \| title=Orphan Drug Act of 1983 \| work=US Food and Drug Administration \| date=4 January 1983 \| accessdate=27 October 2015}}</ref>		In 1985 the ] pimozide (brand name Orap) was approved by the U.S. ] (FDA or USFDA) for marketing in the U.S. for the treatment of ] (TS)<ref name="Pimozide_1985">{{cite journal \|journal = Drug Intell Clin Pharm \|date = June 1985 \|volume = 19 \|number = 6 \|pages = 421–4 \|title = Pimozide: use in Tourette's syndrome \|author1 = Colvin CL \|author2 = Tankanow RM \|pmid = 3891283 }}</ref> — one of a number of rare diseases — which also included ], ], ], and ] — in the United States ], a law enacted to facilitate development of orphan drugs for conditions which affect small numbers of individuals residing in the United States.<ref name="GPO">{{cite web \|url = http://www.gpo.gov/fdsys/pkg/STATUTE-96/pdf/STATUTE-96-Pg2049.pdf \|title = Orphan Drug Act of 1983 \|work = US Food and Drug Administration \|date = 4 January 1983 \|accessdate = 27 October 2015 }}</ref>

		⚫	== See also ==

			{{Portal\|Medicine}}

⚫	==See also==
	* ]		* ]
	* ]		* ]

	== Notes ==		== Notes ==

	{{reflist\|group=Note}}		{{reflist\|group=Note}}

	== References ==		== References ==

	{{Reflist}}		{{Reflist}}

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Revision as of 12:17, 27 November 2017

Pharmaceutical compound

Pimozide
Clinical data

Trade names	Orap
AHFS/Drugs.com	Monograph
MedlinePlus	a686018
License data	US FDA: Pimozide
Pregnancy category	AU: B1
Routes of administration	Oral
ATC code	N05AG02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	40-50%
Metabolism	CYP3A4, CYP1A2 and CYP2D6
Elimination half-life	55 hours (adults), 66 hours (children)
Excretion	Urine
Identifiers
IUPAC name 1--4-piperidinyl]-1,3-dihydro-2H-benzimidazole-2-one
CAS Number	2062-78-4
PubChem CID	16362
IUPHAR/BPS	90
DrugBank	DB01100
ChemSpider	15520
UNII	1HIZ4DL86F
KEGG	D00560
ChEBI	CHEBI:8212
ChEMBL	ChEMBL1423
CompTox Dashboard (EPA)	DTXSID8023474
ECHA InfoCard	100.016.520
Chemical and physical data
Formula	C₂₈H₂₉F₂N₃O
Molar mass	461.56 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES Fc1ccc(cc1)C(c2ccc(F)cc2)CCCN5CCC(N4c3ccccc3NC4=O)CC5
InChI InChI=1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34) Key:YVUQSNJEYSNKRX-UHFFFAOYSA-N
(verify)

Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, and, more rarely, neuroleptic malignant syndrome and prolongation of the QT interval.

Medical uses

Pimozide is used in its oral preparation in schizophrenia and chronic psychosis (on-label indications in Europe only), Tourette syndrome and resistant tics (Europe, USA and Canada).

Pimozide has been used in the treatment of delusional disorder and paranoid personality disorder. It has also been used for delusions of parasitosis.

Use as an antibiotic for Listeria monocytogenes has been described.

It has also been used once in the treatment of gender dysphoria, although whether the patient has since experienced remission is unknown. And it is recommended to be considered in cases of "doubtful gender dysphoria".

Side effects

Very common (>10% frequency) side effects include:

Akinesia
Constipation
Dizziness
Dry mouth
Hyperhidrosis
Nocturia
Somnolence
Speech disorder

Contraindications

It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation. Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or torsades de pointes. Likewise its use is also advised against in individuals with uncorrected hypokalaemia and hypomagnesaemia or clinical significant cardiac disorders (e.g. a recent myocardial infarction or bradycardia. It is also contraindicated in individuals being cotreated with SSRIs or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives. Likewise its use is contraindicated in individuals receiving treatment with CYP3A4, CYP1A2, or CYP2D6 inhibitors.

Overdose

Pimozide overdose presents with severe extrapyramidal symptoms, hypotension, sedation, QT interval prolongation and ventricular arrhythmias including torsades de pointes. Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose. Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.

Efficacy

A 2013 systematic review compared pimozide with other antipsychotics for schizophrenia or related psychoses:

Pimozide versus any other antipsychotic

Summary

Enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with effectiveness similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia.

Outcome	Findings in words	Findings in numbers	Quality of evidence
Global state
Relapse Follow-up: average 38 weeks	These is no clear difference between pimozide and other antipsychotic drugs. Data supporting this finding are based on moderate quality evidence.	RR 0.82 (0.57 to 1.17)	Moderate
Mental state
No improvement Follow-up: 16 weeks	There is not a clear difference between pimozide and other antipsychotic drugs for this mental state outcome but data supporting this finding are very limited.	RR 1.09 (0.08 to 15.41)	Very low
Presence of first-rank symptoms Follow-up: 3-12 months	Pimozide may reduce the chance of experiencing these problematic symptoms but there is no clear difference between people given pimozide and those receiving any other antipsychotic. These findings are based on data of low quality.	RR 0.53 (0.25 to 1.11)	Low
Adverse effects – Extrapyramidal adverse effects
Parkinsonism (rigidity) Follow-up: mean 14 weeks	In the short term these is no clear difference between pimozide and other antipsychotic drugs for this adverse effect. These findings are based on data of low quality. There are no data in the longer term.	RR 1.25 (0.37 to 4.17)	Low
Parkinsonism (tremor) Follow-up: mean 29 weeks	There is no clear difference between pimozide and other antipsychotic drugs for the adverse effect of causing tremor but these findings are based on data of low quality.	RR 1.45 (0.68 to 3.09)	Low
Missing outcomes
	The outcome of quality of life was not measured/reported in the included studies.

Pharmacology

Pimozide acts as an antagonist of the D₂, D₃, and D₄ receptors and the 5-HT₇ receptor. It is also a hERG blocker.

Similarly to other typical antipsychotics pimozide has a high affinity for the Dopamine D₂ receptor and this likely results in its sexual (due to prolactin hypersecretion) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of schizophrenia.

Binding profile
Protein	K_i (nM)	Notes
5-HT_1A	650
5-HT_2A	48.4	This receptor is believed to be responsible for the atypicality of other antipsychotics like clozapine, olanzapine and quetiapine. Pimozide's affinity towards this receptor is low compared to its affinity for the D₂ receptor and hence this receptor unlikely contributes to its effects to any meaningful extent.
5-HT_2C	2,112
5-HT₆	71
5-HT₇	0.5	Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.
α_1A	197.7	Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension.
α_2A	1,593
α_2B	821
α_2C	376.5
M₃	1,955	This receptor is believed to be responsible for the interference with glucose homeostasis seen with some of the atypical antipsychotics such as clozapine and olanzapine. Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis.
D₁	>10,000
D₂	0.33	Likely the receptor responsible for the therapeutic effects against the positive symptoms of schizophrenia of antipsychotics like pimozide as well as the prolactin-elevating and extrapyramidal side effect-generating effects of typical antipsychotics like pimozide.
D₃	0.25
D₄	1.8
hERG	18	May be responsible for pimozide's high liability for prolonging the QT interval.
H₁	692	Likely responsible for why pimozide tends to produce so little sedation.
σ	508

Pharmacokinetic data
Pharmacokinetic parameter	Value
Time to peak plasma concentration (T_max)	6-8 hr
Peak plasma concentration (C_max)	4-19 ng/mL
Elimination half-life (t_1/2)	55 hours (adults), 66 hours (children)
Metabolising enzymes	CYP3A4, CYP1A2 and CYP2D6
Excretion pathways	Urine

Orphan Drug 1985

In 1985 the orphan drug pimozide (brand name Orap) was approved by the U.S. Food and Drug Administration (FDA or USFDA) for marketing in the U.S. for the treatment of Tourette's syndrome (TS) — one of a number of rare diseases — which also included Huntington's Disease, myoclonus, ALS, and muscular dystrophy — in the United States Orphan Drug Act of 1983, a law enacted to facilitate development of orphan drugs for conditions which affect small numbers of individuals residing in the United States.

Notes

A lower K_i value indicates a stronger binding

References

Munro, A. (1999)Delusional disorder. Cambridge: Cambridge University Press. ISBN 0-521-58180-X.
van Vloten WA (March 2003). "Pimozide: use in dermatology". Dermatol. Online J. 9 (2): 3. PMID 12639456.
Lieberman LA, Higgins DE (February 2009). "A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection". Antimicrob. Agents Chemother. 53 (2): 756–64. doi:10.1128/AAC.00607-08. PMC 2630664. PMID 19015342.
B. K. Puri, MA, MB, BChir. MRCPsychResearch Fellow, I. Singh, MBBS. FRCPsych (June 1996). "Pharmacotherapy with pimozide should be considered in cases of doubtful gender dysphoria". Australian & New Zealand Journal of Psychiatry. 30 (3): 422-425. doi:10.3109/00048679609065010. PMID 8839957.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ "Oral (pimozide) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 4 December 2013.
^ "Oral 4 mg tablets. - Summary of Product Characteristics". electronic Medicines Compendium. Janssen-Cilag Ltd. 2 April 2013. Archived from the original on 3 March 2016. Retrieved 4 December 2013. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Brayfield, A (12 February 2013). Pimozide. London, UK: Pharmaceutical Press. Retrieved 4 December 2013. {{cite book}}: |work= ignored (help)
^ "ORAP (pimozide) tablet [Teva Select Brands]". DailyMed. Teva Select Brands. July 2012. Retrieved 4 December 2013.
^ Mothi, M; Sampson, S (2013). "Pimozide for schizophrenia or related psychoses". Cochrane Database of Systematic Reviews. 11: CD001949.pub3. doi:10.1002/14651858.CD001949.pub3.
^ Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.{{cite book}}: CS1 maint: multiple names: authors list (link)
Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 4 December 2013.
"Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression" (PDF). Indian Journal of Pharmaceutical Education and Research. 45 (1): 46–53. January–March 2011.
^ Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
Colvin CL; Tankanow RM (June 1985). "Pimozide: use in Tourette's syndrome". Drug Intell Clin Pharm. 19 (6): 421–4. PMID 3891283.
"Orphan Drug Act of 1983" (PDF). US Food and Drug Administration. 4 January 1983. Retrieved 27 October 2015.

External links

v t e Antipsychotics (N05A)
Typical	Butyrophenones: Benperidol Bromperidol Bromperidol decanoate Droperidol Haloperidol Haloperidol decanoate Moperone Pipamperone Spiperone Timiperone Trifluperidol Diphenylbutylpiperidines: Fluspirilene Penfluridol Pimozide Phenothiazines: Acepromazine Acetophenazine Butaperazine Carphenazine (carfenazine) Chlorpromazine Cyamemazine Dixyrazine Fluphenazine Fluphenazine decanoate Fluphenazine enanthate Levomepromazine (methotrimeprazine) Mesoridazine Perazine Periciazine Perphenazine BL-1020 Perphenazine decanoate Perphenazine enanthate Piperacetazine Pipotiazine Pipotiazine palmitate Pipotiazine undecylenate Prochlorperazine Promazine Sulforidazine Thiopropazate Thioproperazine Thioridazine Trifluoperazine Triflupromazine Thioxanthenes: Chlorprothixene Clopenthixol Clopenthixol decanoate Flupentixol Flupentixol decanoate Tiotixene (thiothixene) Zuclopenthixol Zuclopenthixol acetate Zuclopenthixol decanoate
Disputed	Benzamides: Amisulpride Levosulpiride Nemonapride Remoxipride Sulpiride Sultopride Tiapride Veralipride Butyrophenones: Melperone Tricyclics: Carpipramine Clocapramine Clorotepine Clotiapine Loxapine Mosapramine Oxyprothepin decanoate Others: Molindone
Atypical	Benzisoxazole/benzisothiazoles: Iloperidone Lurasidone Paliperidone Paliperidone palmitate Perospirone Risperidone Ziprasidone Butyrophenones: Lumateperone Phenylpiperazines/quinolinones: Aripiprazole Aripiprazole lauroxil Brilaroxazine Brexpiprazole Cariprazine Tricyclics: Asenapine Clozapine Olanzapine (+samidorphan) Quetiapine Zotepine Others: Blonanserin Pimavanserin Sertindole
Others	Monoamine-depleting agents: Oxypertine Reserpine Tetrabenazine Muscarinic agonists: Xanomeline/trospium chloride Others/unknown: Azacyclonol
WHO-EM Withdrawn from market Clinical trials: Phase III Never to phase III

Pharmacodynamics

Dopamine receptor modulators

D₁-like

Agonists

Phenethylamines: BCO-001
Deoxyepinephrine (N-methyldopamine, epinine)
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Etilevodopa
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XP21279

PAMs

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Antagonists

Typical antipsychotics: Butaclamol
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D₂-like

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Atypical antipsychotics: Alentemol (U-66444B)
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Aripiprazole lauroxil
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Antagonists

Typical antipsychotics: Acepromazine
Acetophenazine
Azaperone
Benperidol
Bromperidol
Butaclamol
Butaperazine
Chloracizine
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Chlorpromazine
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Fluspirilene
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Sarakalim

GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: ML-297 (VU0456810)

K_CaTooltip Calcium-activated potassium channel

Blockers	BK_Ca-specific: Ethanol (alcohol) GAL-021
Activators	BK_Ca-specific: Flufenamic acid Meclofenamic acid Niflumic acid Nimesulide Rottlerin (mallotoxin) Tolfenamic acid

K2PsTooltip Tandem pore domain potassium channel

Blockers	12-O-Tetradecanoylphorbol-13-acetate Arachidonic acid Fluoxetine Norfluoxetine
Activators	Riluzole

Sodium

VGSCsTooltip Voltage-gated sodium channels

Blockers

Antianginals: Ranolazine

Local anesthetics: pFBT
Amylocaine
Articaine
Benzocaine
Bupivacaine (Levobupivacaine, Ropivacaine)
Butacaine
Butamben
Chloroprocaine
Cinchocaine
Cocaine
Cyclomethycaine
Dimethocaine
Diphenhydramine
Etidocaine
Hexylcaine
Iontocaine
Lidocaine
Mepivacaine
Meprylcaine
Metabutoxycaine
Orthocaine
Piperocaine
Prilocaine
Procaine
Propoxycaine
Proxymetacaine
Risocaine
Tetracaine
Trimecaine

Activators

Aconitine
Atracotoxins (ω-Atracotoxin, Robustoxin, Versutoxin)
Batrachotoxin
Ciguatoxins
Grayanotoxins
Poneratoxin

ENaCTooltip Epithelial sodium channel

Blockers	Amiloride Benzamil Triamterene
Activators	Solnatide

ASICsTooltip Acid-sensing ion channel

Blockers	A-317567 Amiloride Aspirin Ibuprofen PcTX1

Chloride

CaCCsTooltip Calcium-activated chloride channel

Blockers	Crofelemer DIDS Ethacrynic acid Flufenamic acid Fluoxetine Furosemide Glibenclamide Mefloquine Mibefradil Niflumic acid
Activators	Carbachol

CFTRTooltip Cystic fibrosis transmembrane conductance regulator

Blockers	Glibenclamide Lonidamine Piretanide
Activators	1,7-Phenanthroline 1,10-Phenanthroline 4,7-Phenanthroline 7,8-Benzoquinoline Ivacaftor Phenanthridine

Unsorted

Blockers	Bumetanide Flufenamic acid Meclofenamic acid Mefenamic acid Mepacrine Niflumic acid Talniflumate Tolfenamic acid Trifluoperazine

Others

TRPsTooltip Transient receptor potential channels	See here instead.
LGICsTooltip Ligand gated ion channels	See here instead.

See also: Receptor/signaling modulators • Transient receptor potential channel modulators

Serotonin receptor modulators

5-HT₁

5-HT_1A

Agonists: 8-OH-DPAT Adatanserin Amphetamine Antidepressants (e.g., etoperidone, hydroxynefazodone, nefazodone, trazodone, triazoledione, vilazodone, vortioxetine) Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, lurasidone, quetiapine, ziprasidone) Azapirones (e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone) Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Dopamine Ebalzotan Eltoprazine Enciprazine Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, LSD, methylergometrine (methylergonovine), methysergide, pergolide) F-11,461 F-12826 F-13714 F-14679 F-15063 F-15,599 Flesinoxan Flibanserin Flumexadol Hypidone Lesopitron LY-293284 LY-301317 mCPP MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S-14,506 S-14671 S-15535 Sarizotan Serotonin (5-HT) SSR-181507 Sunepitron Tryptamines (e.g., 5-CT, 5-MeO-DMT, 5-MT, bufotenin, DMT, indorenate, N-Me-5-HT, psilocin, psilocybin) TGBA01AD U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone, risperidone, sertindole) AV965 Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, pindolol, propranolol, tertatolol) BMY-7,378 CSP-2503 Dotarizine Ergolines (e.g., metergoline) FCE-24379 Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine (methiothepin) MIN-117 (WF-516) MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100135 WAY-100635 Xylamidine
Unknown/unsorted: Acetryptine Carvedilol Ergolines (e.g., ergometrine (ergonovine))

5-HT_1B

Agonists: Anpirtoline CGS-12066A CP-93129 CP-94253 CP-122,288 CP-135807 Eltoprazine Ergolines (e.g., bromocriptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) mCPP RU-24,969 Serotonin (5-HT) Triptans (e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan) TFMPP Tryptamines (e.g., 5-BT, 5-CT, 5-MT, DMT) Vortioxetine
Antagonists: AR-A000002 Beta blockers (e.g., alprenolol, carteolol, isamoltane, oxprenolol, penbutolol, propranolol, tertatolol) Elzasonan Ergolines (e.g., metergoline) GR-127935 Isamoltane LY-393558 Metitepine (methiothepin) SB-216641 SB-224289 SB-236057 Yohimbine
Unknown/unsorted: Ergolines (e.g., cabergoline, ergometrine (ergonovine), lisuride)

5-HT_1D

Agonists: CP-122,288 CP-135807 CP-286601 Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, LSD, methysergide) GR-46611 L-694247 L-772405 mCPP PNU-109291 PNU-142633 Serotonin (5-HT) TGBA01AD Triptans (e.g., almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) Tryptamines (e.g., 5-BT, 5-CT, 5-Et-DMT, 5-MT, 5-(nonyloxy)tryptamine, DMT)
Antagonists: Alniditan BRL-15,572 Elzasonan Ergolines (e.g., metergoline) GR-127935 Ketanserin LY-310762 LY-367642 LY-393558 LY-456219 LY-456220 Metitepine (methiothepin) Mianserin Ritanserin Yohimbine Ziprasidone
Unknown/unsorted: Acetryptine Ergolines (e.g., lisuride, lysergol, pergolide)

5-HT_1E

Agonists: BRL-54443 Ergolines (e.g., methysergide) Serotonin (5-HT) Triptans (e.g., eletriptan) Tryptamines (e.g., tryptamine)
Antagonists: Metitepine (methiothepin)
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine), lysergol, methylergometrine (methylergonovine)

5-HT_1F

Agonists: BRL-54443 CP-122,288 Ergolines (e.g., bromocriptine, lysergol, methylergometrine (methylergonovine) methysergide) Lasmiditan LY-334370 Serotonin (5-HT) Triptans (e.g., eletriptan, naratriptan, sumatriptan) Tryptamines (e.g., 5-MT)
Antagonists: Metitepine (methiothepin) Mianserin

5-HT₂

5-HT_2A

Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN-NBOH, 2CBFly-NBOMe) 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 2C-B-FLY 2CB-Ind 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) AL-34662 AL-37350A Bromo-DragonFLY Dimemebfe DMBMPP DOx (e.g., DOB, DOC, DOI, DOM) Efavirenz Ergolines (e.g., 1P-LSD, ALD-52, bromocriptine, cabergoline, ergine (LSA), ergometrine (ergonovine), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, methylergometrine (methylergonovine), pergolide) Flumexadol IHCH-7113 Jimscaline Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) O-4310 Oxaflozane PHA-57378 PNU-22394 PNU-181731 RH-34 SCHEMBL5334361 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., BZP, quipazine, TFMPP) Serotonin (5-HT) TCB-2 TFMFly Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: 5-I-R91150 5-MeO-NBpBrT AC-90179 Adatanserin Altanserin Antihistamines (e.g., cyproheptadine, hydroxyzine, ketotifen, perlapine) AMDA Atypical antipsychotics (e.g., amperozide, aripiprazole, asenapine, blonanserin, brexpiprazole, carpipramine, clocapramine, clorotepine, clozapine, fluperlapine, gevotroline, iloperidone, lurasidone, melperone, mosapramine, ocaperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zicronapine, ziprasidone, zotepine) Chlorprothixene Cinanserin CSP-2503 Deramciclane Dotarizine Eplivanserin Ergolines (e.g., amesergide, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Fananserin Flibanserin Glemanserin Irindalone Ketanserin KML-010 Landipirdine LY-393558 mCPP Medifoxamine Metitepine (methiothepin) MIN-117 (WF-516) Naftidrofuryl Nantenine Nelotanserin Opiranserin (VVZ-149) Pelanserin Phenoxybenzamine Pimavanserin Pirenperone Pizotifen Pruvanserin Rauwolscine Ritanserin Roluperidone S-14671 Sarpogrelate Serotonin antagonists and reuptake inhibitors (e.g., etoperidone, hydroxynefazodone, lubazodone, mepiprazole, nefazodone, triazoledione, trazodone) SR-46349B TGBA01AD Teniloxazine Temanogrel Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline) Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, setoperone, spiperone, spiramide, thioridazine, thiothixene, trifluoperazine) Volinanserin Xylamidine Yohimbine
Unknown/unsorted: Ergolines (e.g., dihydroergotamine, nicergoline)

5-HT_2B

Agonists: 4-Methylaminorex Aminorex Amphetamines (e.g., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine) BW-723C86 DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) Piperazines (e.g., TFMPP) PNU-22394 Ro60-0175 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, 5-MT, α-Me-5-HT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: Agomelatine Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, N-desalkylquetiapine (norquetiapine), N-desmethylclozapine (norclozapine), olanzapine, pipamperone, quetiapine, risperidone, ziprasidone) Cyproheptadine EGIS-7625 Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine) Ketanserin LY-393558 mCPP Metadoxine Metitepine (methiothepin) Pirenperone Pizotifen Propranolol PRX-08066 Rauwolscine Ritanserin RS-127445 Sarpogrelate SB-200646 SB-204741 SB-206553 SB-215505 SB-221284 SB-228357 SDZ SER-082 Tegaserod Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Trazodone Typical antipsychotics (e.g., chlorpromazine) TIK-301 Yohimbine
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine))

5-HT_2C

Agonists: 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) A-372159 AL-38022A Alstonine CP-809101 Dimemebfe DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide) Flumexadol Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) MK-212 ORG-12962 ORG-37684 Oxaflozane PHA-57378 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP) PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine) Vabicaserin WAY-629 WAY-161503 YM-348
Antagonists: Adatanserin Agomelatine Atypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine) Captodiame CEPC Cinanserin Cyproheptadine Deramciclane Desmetramadol Dotarizine Eltoprazine Ergolines (e.g., amesergide, bromocriptine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Etoperidone Fluoxetine FR-260010 Irindalone Ketanserin Ketotifen Latrepirdine (dimebolin) Medifoxamine Metitepine (methiothepin) Nefazodone Pirenperone Pizotifen Propranolol Ritanserin RS-102221 S-14671 SB-200646 SB-206553 SB-221284 SB-228357 SB-242084 SB-243213 SDZ SER-082 Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) TIK-301 Tramadol Trazodone Tricyclic antidepressants (e.g., amitriptyline, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine) Xylamidine
Unknown/unsorted: Efavirenz Ergolines (e.g., ergometrine (ergonovine), methylergometrine (methylergonovine))

5-HT₃_–7

5-HT₃

Agonists: Alcohols (e.g., butanol, ethanol (alcohol), trichloroethanol) m-CPBG Phenylbiguanide Piperazines (e.g., BZP, mCPP, quipazine) RS-56812 Serotonin (5-HT) SR-57227 SR-57227A Tryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ)) Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane) YM-31636
Antagonists: Alosetron Anpirtoline Arazasetron AS-8112 Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine) Azasetron Batanopride Bemesetron (MDL-72222) Bupropion Cilansetron CSP-2503 Dazopride Dolasetron Galanolactone Granisetron Hydroxybupropion Lerisetron Memantine Ondansetron Palonosetron Ramosetron Renzapride Ricasetron Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Thujone Tropanserin Tropisetron Typical antipsychotics (e.g., loxapine) Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon) Vortioxetine Zacopride Zatosetron
Unknown/unsorted: LY-53857 Piperazines (e.g., naphthylpiperazine)

5-HT₄

Agonists: 5-MT BIMU8 Capeserod Cinitapride Cisapride CJ-033466 Dazopride Metoclopramide Minesapride Mosapride Prucalopride PRX-03140 Renzapride RS-67,333 RS-67,506 Serotonin (5-HT) Tegaserod Usmarapride Velusetrag Zacopride
Antagonists: GR-113808 GR-125487 L-Lysine Piboserod RS-39604 RS-67532 SB-203186 SB-204070

5-HT_5A

Agonists: Ergolines (e.g., 2-Br-LSD (BOL-148), ergotamine, LSD)
Serotonin (5-HT)
Tryptamines (e.g., 5-CT)
Valerenic acid

Unknown/unsorted: Ergolines (e.g., metergoline, methysergide)
Piperazines (e.g., naphthylpiperazine)

5-HT₆

Agonists: Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide) Hypidone Serotonin (5-HT) Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, ST-1936, tryptamine) WAY-181187 WAY-208466
Antagonists: ABT-354 Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone) AVN-101 AVN-211 AVN-322 AVN-397 BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742457 Idalopirdine Ketanserin Landipirdine Latrepirdine (dimebolin) Masupirdine Metitepine (methiothepin) MS-245 PRX-07034 Ritanserin Ro 04-6790 Ro 63-0563 SB-258585 SB-271046 SB-357134 SB-399885 SB-742457 Tetracyclic antidepressants (e.g., amoxapine, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine)
Unknown/unsorted: Ergolines (e.g., 2-Br-LSD (BOL-148), bromocriptine, lergotrile, pergolide) Piperazines (e.g., naphthylpiperazine)

5-HT₇

Agonists: 8-OH-DPAT AS-19 Bifeprunox E-55888 Ergolines (e.g., LSD) LP-12 LP-44 LP-211 RU-24,969 Sarizotan Serotonin (5-HT) Triptans (e.g., frovatriptan) Tryptamines (e.g., 5-CT, 5-MT, bufotenin, N-Me-5-HT)
Antagonists: Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine) Butaclamol DR-4485 EGIS-12,233 Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) JNJ-18038683 Ketanserin LY-215,840 Metitepine (methiothepin) Ritanserin SB-258719 SB-258741 SB-269970 SB-656104 SB-656104A SB-691673 SLV-313 SLV-314 Spiperone SSR-181507 Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine) Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide) Vortioxetine
Unknown/unsorted: Ergolines (e.g., lisuride, pergolide) Piperazines (e.g., naphthylpiperazine)

See also: Receptor/signaling modulators
Adrenergics
Dopaminergics
Melatonergics
Monoamine reuptake inhibitors and releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins

v t e Sigma receptor modulators
σ₁	Agonists: 3-PPP 4-PPBP 5-MeO-DMT Alazocine (SKF-10047) Amantadine Arketamine BD-737 BD-1052 Blarcamesine Captodiame Citalopram CGRPTooltip Calcitonin gene-related peptide Cloperastine Cocaine Cutamesine (SA-4503) Cyclazocine Dehydroepiandrosterone (DHEA) (prasterone) Dehydroepiandrosterone sulfate (DHEA-S) (prasterone sulfate) Dextrallorphan Dextromethorphan (DXM) Dextrorphan (DXO) Dimemorfan Dimethyltryptamine (DMT) Ditolylguanidine (DTG) Donepezil Eliprodil Escitalopram Fabomotizole (afobazole) Fluoxetine Fluvoxamine Ifenprodil Igmesine (JO-1784) IPAB Ketamine L-687384 MDMA (midomafetamine) Memantine Methamphetamine Methoxetamine Methylphenidate Nepinalone Neuropeptide Y Noscapine OPC-14523 Opipramol Pentazocine Pentoxyverine (carbetapentane) PRE-084 Pregnenolone Pregnenolone sulfate Pridopidine Racemethorphan (methorphan) Racemorphan (morphanol) UMB-23 UMB-82 Antagonists: 3-PPP AC-927 BD-1008 BD-1031 BD-1047 BD-1060 BD-1063 BD-1067 BMY-14802 (BMS-181100) CM-156 Dup-734 E-5842 E-52862 (S1RA) Haloperidol LR-132 LR-172 MS-377 NE-100 NPC-16377 Panamesine (EMD-57455) PD-144418 Pentazocine Progesterone Rimcazole (BW-234U) Sertraline SR-31742A Allosteric modulators: Phenytoin; Positive: Methylphenylpiracetam SOMCL-668 Unknown/unsorted: 3-Methoxydextrallorphan 3-MeO-PCP 4C-T-2 4-IBP 4-IPBS 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Amitriptyline Azidopamil Chlorpromazine Clemastine Clomipramine Clorgiline D-Deprenyl DiPTTooltip N,N-Diisopropyltryptamine DPTTooltip N,N-Dipropyltryptamine Ibogaine Imipramine KCR-12-83.1 Nemonapride Noribogaine RHL-033 RS-67,333 RTI-55 Saffron Safinamide Selegiline Spipethiane Trifluoperazine W-18 YKP10A
σ₂	Agonists: 3-PPP Arketamine BD-1047 BD1063 Ditolylguanidine (DTG) DKR-1005 DKR-1051 Haloperidol Ifenprodil Ketamine MDMA (midomafetamine) Methamphetamine OPC-14523 Opipramol PB-28 Phencyclidine Siramesine (Lu 28-179) UKH-1114 Antagonists: AC-927 BD-1008 BD-1067 CM-156 CT-1812 LR-172 MIN-101 Panamesine (EMD-57455) SAS-0132 Unknown/unsorted: 3-Methoxydextrallorphan 3-MeO-PCE 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Clemastine DiPTTooltip N,N-Diisopropyltryptamine DPTTooltip N,N-Dipropyltryptamine Ibogaine Lu 29-252 Nemonapride Nepinalone Noribogaine Pentazocine RS-67,333 Safinamide TMATooltip 3,4,5-Trimethoxyamphetamine UMB-23 UMB-82 W-18
Unsorted	Agonists: Berberine Ethylketazocine Fourphit Metaphit Naluzotan Tapentadol Tenocyclidine Antagonists: AHD1 AZ66 Lamotrigine Naloxone SM-21 UMB-100 UMB-101 UMB-103 UMB-116 YZ-011 YZ-069 YZ-185 Allosteric modulators: SKF-83959 Unknown/unsorted: 18-Methoxycoronaridine BMY-13980 Butaclamol Caramiphen Carvotroline Chlorphenamine (chlorpheniramine) Chlorpromazine Cinnarizine Cinuperone Clocapramine Dezocine EMD-59983 Hypericin (St. John's wort) Fluphenazine Gevotroline (WY-47384) Mepyramine (pyrilamine) Molindone Perphenazine Pimozide Proadifen Promethazine Propranolol Quinidine Remoxipride SL 82.0715 SR-31747A Tiospirone (BMY-13859) Venlafaxine
See also: Receptor/signaling modulators

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