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Revision as of 08:08, 20 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit		Latest revision as of 07:13, 18 December 2024 edit undoPashihiko (talk | contribs)Extended confirmed users3,559 editsNo edit summary
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			{{Short description|Medication for movement disorders}}
	<!---Please DO NOT move this page to "benztropine" without discussion. Benztropine is the International Nonproprietary Name and should be used according to WP:MEDMOS and WP:PHARM guidelines!-->
			{{Use dmy dates|date=March 2024}}
	{{drugbox | Verifiedfields = changed
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	| verifiedrevid = 401818096
			<!-- Please DO NOT move this page to "benztropine" without discussion. Benzatropine is the International Nonproprietary Name and should be used according to WP:MEDMOS and WP:PHARM guidelines! -->
	| IUPAC_name = (3-''endo'')-3-(diphenylmethoxy)-8-methyl-8-azabicyclooctane
			{{drugbox
	| image = Benztropine.png
			| Verifiedfields = changed
	| drug_name = Benztropine
			| Watchedfields = changed
			| class = ]
	<!--Clinical data-->
			| verifiedrevid = 456483119
	| tradename = Cogentin
			| IUPAC_name = (3-''endo'')-3-(Diphenylmethoxy)-8-methyl-8-azabicyclooctane
	| Drugs.com = {{drugs.com|monograph|cogentin}}
			| image = Benzatropine.svg
	| pregnancy_US = C
			| alt =
			| image2 = Benzatropina.gif
			| alt2 = <!-- Clinical data -->
			| tradename = Cogentin, others
			| Drugs.com = {{drugs.com|monograph|benztropine-mesylate}}
			| DailyMedID = Benztropine
			| pregnancy_AU = B2
	| pregnancy_category =		| pregnancy_category =
			| routes_of_administration = ], ], ]
	| legal_status =
			| ATC_prefix = N04
	| routes_of_administration = Oral, ], ]
			| ATC_suffix = AC01
			| legal_AU = S4
			| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024 | archive-date=6 July 2023 | archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | url-status=live }}</ref>
			| legal_US = Rx-only
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->| bioavailability =
			| metabolism = ]
	| bioavailability =
			| elimination_half-life = 12–24 hours
	| metabolism =
			| duration_of_action = 10 hours
	| elimination_half-life =
	| excretion =		| excretion = ]
	<!--Identifiers-->		<!--Identifiers-->| IUPHAR_ligand = 7601
	| CASNo_Ref = {{cascite|correct|CAS}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 86-13-5		| CAS_number = 86-13-5
	| ATC_prefix = N04
	| ATC_suffix = AC01
	| PubChem = 1201549		| PubChem = 1201549
			| KEGG = D07511
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
	| DrugBank = <!-- blanked - oldvalue: DB00245 -->
			| DrugBank = DB00245
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 16736541		| ChemSpiderID = 16736541
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 1NHL2J4X8K		| UNII = 1NHL2J4X8K
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 3048		| ChEBI = 3048
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| ChEMBL = <!-- blanked - oldvalue: 1201203 -->		| ChEMBL = 1201203
			<!--Chemical data-->| C = 21
	| C=21 | H=25 | N=1 | O=1
			| H = 25
	| molecular_weight = 307.429 g/mol
			| N = 1
			| O = 1
	| smiles = CN41CC4C(C1)OC(c2ccccc2)c3ccccc3		| smiles = CN41CC4C(C1)OC(c2ccccc2)c3ccccc3
	| InChI = 1/C21H25NO/c1-22-18-12-13-19(22)15-20(14-18)23-21(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-21H,12-15H2,1H3/t18-,19+,20+
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C21H25NO/c1-22-18-12-13-19(22)15-20(14-18)23-21(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-21H,12-15H2,1H3/t18-,19+,20+		| StdInChI = 1S/C21H25NO/c1-22-18-12-13-19(22)15-20(14-18)23-21(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-21H,12-15H2,1H3/t18-,19+,20+
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = GIJXKZJWITVLHI-PMOLBWCYSA-N		| StdInChIKey = GIJXKZJWITVLHI-PMOLBWCYSA-N
			| USAN = benztropine
			| BAN = benzatropine
	}}		}}
			<!-- Definition and medical uses -->
			'''Benzatropine''' (]),<ref name="INN">{{cite journal |author=World Health Organization |date=December 1959 |title=International Non-Proprietary Names for Pharmaceutical Preparations). Recommended International Non-Proprietary Names (Rec. I.N.N.): List 3º |url=https://www.who.int/medicines/publications/druginformation/innlists/RL03.pdf?ua=1 |url-status=live |journal=WHO Chronicle |volume=13 |issue=12 |page=464 |archive-url=https://web.archive.org/web/20210828062354/https://www.who.int/medicines/publications/druginformation/innlists/RL03.pdf?ua=1 |archive-date=28 August 2021 |access-date=1 December 2020}}</ref> known as '''benztropine''' in the United States and Japan,<ref name="MedNet">{{cite web |author=World Health Organization |title=INN: Benzatropine |url=https://mednet-communities.net/inn/db/ViewINN.aspx?i=292 |url-access=registration |work=WHO MedNet |access-date=1 December 2020 }}{{Dead link|date=January 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> is a medication used to treat ]s like ] and ], as well as ] of ], including ].<ref name="AHFS2019" /> It is not useful for ].<ref name="AHFS2019" /> It is taken by mouth or by ] or ].<ref name="AHFS2019">{{cite web |title=Benztropine Mesylate Monograph for Professionals |url=https://www.drugs.com/monograph/benztropine-mesylate.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=9 April 2019 |language=en |archive-date=6 June 2019 |archive-url=https://web.archive.org/web/20190606064101/https://www.drugs.com/monograph/benztropine-mesylate.html |url-status=live }}</ref> Benefits are seen within two hours and last for up to ten hours.<ref>{{cite book | vauthors = Pagliaro LA, Pagliaro AM |title=PNDR, Psychologists' Neuropsychotropic Drug Reference |date=1999 |publisher=Psychology Press |isbn=9780876309568 |page=47 |url=https://books.google.com/books?id=h_edjWaBilsC&pg=PA47 |language=en}}</ref><ref>{{cite book | vauthors = Aschenbrenner DS, Venable SJ |title=Drug Therapy in Nursing |date=2009 |publisher=Lippincott Williams & Wilkins |isbn=9780781765879 |page=197 |url=https://books.google.com/books?id=5zd_W_PUwvYC&pg=PA197 |language=en}}</ref>
	'''Benzatropine''' (]), also known as '''benztropine''' (], ]), is an ] marketed under the ] '''Cogentin''' which is used in the treatment of ], ], ], and ].
			<!-- Side effects and mechanism -->
	== Indications ==
			Common side effects include ], ], ], and ].<ref name="AHFS2019" /> Serious side effect may include ], ], ], and ].<ref name="AHFS2019" /> It is unclear if use during ] or ] is safe.<ref>{{cite web |title=Benztropine (Cogentin) Use During Pregnancy |url=https://www.drugs.com/pregnancy/benztropine.html |website=Drugs.com |access-date=9 April 2019 |language=en |archive-date=6 June 2019 |archive-url=https://web.archive.org/web/20190606064101/https://www.drugs.com/pregnancy/benztropine.html |url-status=live }}</ref> Benzatropine is an ] which works by ] of ]s.<ref name="AHFS2019" />
			<!-- History and culture -->
	Benzatropine is used in patients to reduce the side effects of ] treatment, such as ] and ]. Benzatropine is also a second-line drug for the treatment of ]. It improves ] and rigidity but not bradykinesia. Benzatropine is also sometimes used for the treatment of ], a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.
			Benzatropine was approved for medical use in the United States in 1954.<ref name=AHFS2019/> It is available as a ].<ref name=AHFS2019/> In 2020, it was the 229th most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022 | archive-date = 12 February 2021 | archive-url = https://web.archive.org/web/20210212142534/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status = live }}</ref><ref>{{cite web | title = Benztropine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Benztropine | access-date = 7 October 2022 | archive-date = 12 May 2023 | archive-url = https://web.archive.org/web/20230512105919/https://clincalc.com/DrugStats/Drugs/Benztropine | url-status = live }}</ref> It is sold under the brand name '''Cogentin''' among others.<ref name=AHFS2019/>
	== Side effects ==		== Medical uses ==
			Benzatropine is used to reduce ] of ] treatment. Benzatropine is also a second-line drug for the treatment of ]. It improves ], and may alleviate ] and ].<ref>{{cite journal | vauthors = DiMascio A, Bernardo DL, Greenblatt DJ, Marder JE | title = A controlled trial of amantadine in drug-induced extrapyramidal disorders | journal = Archives of General Psychiatry | volume = 33 | issue = 5 | pages = 599–602 | date = May 1976 | pmid = 5066 | doi = 10.1001/archpsyc.1976.01770050055008 }}</ref> Benzatropine is also sometimes used for the treatment of ], a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.
			== Adverse effects ==
	These are principally anticholinergic:		These are principally anticholinergic:
	* ]		* ]
	* Blurred vision		* ]
	* Cognitive changes		* Cognitive changes
			* ]
	* ]		* ]
	* ]		* ]
	* ]		* ]
	* ]		* ]
	* ] (in overdose)		* Severe ] and ] (in overdose)
	While some studies suggest that use of anticholinergics increases the risk of ] (a long-term side effect of antipsychotics),<ref>{{cite pmid|6121548}}</ref><ref name="pmid11534539">{{cite journal |author=Wszola BA, Newell KM, Sprague RL |title=Risk factors for tardive dyskinesia in a large population of youths and adults |journal=Experimental and clinical psychopharmacology |volume=9 |issue=3 |pages=285–96 |year=2001 |pmid=11534539|doi=10.1037/1064-1297.9.3.285}}</ref> other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia,<ref name="pmid9546009">{{cite journal |author=van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS |title=Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III |journal=The American journal of psychiatry |volume=155 |issue=4 |pages=565–7 |year=1998 |pmid=9546009 |doi=}}</ref> although symptoms may be worsened.<ref>{{cite journal |pmid=3063514 |year=1988 |last1=Yassa |first1=R |title=Tardive dyskinesia and anticholinergic drugs. A critical review of the literature. |volume=14 Spec No |pages=233–9 |journal=L'Encephale}}</ref>		While some studies suggest that use of ] increases the risk of ] (a long-term side effect of ]),<ref>{{cite journal | vauthors = Kane JM, Smith JM | title = Tardive dyskinesia: prevalence and risk factors, 1959 to 1979 | journal = Archives of General Psychiatry | volume = 39 | issue = 4 | pages = 473–481 | date = April 1982 | pmid = 6121548 | doi = 10.1001/archpsyc.1982.04290040069010 | s2cid = 10194153 }}</ref><ref name="pmid11534539">{{cite journal | vauthors = Wszola BA, Newell KM, Sprague RL | title = Risk factors for tardive dyskinesia in a large population of youths and adults | journal = Experimental and Clinical Psychopharmacology | volume = 9 | issue = 3 | pages = 285–296 | date = August 2001 | pmid = 11534539 | doi = 10.1037/1064-1297.9.3.285 }}</ref> other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia,<ref name="pmid9546009">{{cite journal | vauthors = van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS | title = Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III | journal = The American Journal of Psychiatry | volume = 155 | issue = 4 | pages = 565–567 | date = April 1998 | pmid = 9546009 | doi = 10.1176/ajp.155.4.565 }}</ref> although symptoms may be worsened.<ref>{{cite journal | vauthors = Yassa R | title = Tardive dyskinesia and anticholinergic drugs. A critical review of the literature | journal = L'Encéphale | volume = 14 Spec No | issue = Spec No | pages = 233–239 | date = September 1988 | pmid = 3063514 }}</ref>
			Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception.<ref name="pmid2661606">{{cite journal | vauthors = Gelenberg AJ, Van Putten T, Lavori PW, Wojcik JD, Falk WE, Marder S, Galvin-Nadeau M, Spring B, Mohs RC, Brotman AW | title = Anticholinergic effects on memory: benztropine versus amantadine | journal = Journal of Clinical Psychopharmacology | volume = 9 | issue = 3 | pages = 180–185 | date = June 1989 | pmid = 2661606 | doi = 10.1097/00004714-198906000-00004 | s2cid = 27308127 }}</ref>
	== Pharmacology ==		== Pharmacology ==
			=== Pharmacodynamics ===
			==== Antihistamine and anticholinergic activity ====
			Benzatropine is a ] ] and ]. In terms of its anticholinergic activity, it is specifically an ] and acts a ] ] ] and ] ].<ref name="LakstygalKolesnikovaKhatsko2019">{{cite journal | vauthors = Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV | title = DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens | journal = ACS Chem Neurosci | volume = 10 | issue = 5 | pages = 2144–2159 | date = May 2019 | pmid = 30566832 | doi = 10.1021/acschemneuro.8b00615 | url = }}</ref> Benzatropine partially blocks cholinergic activity in the ]. Animal studies have indicated that anticholinergic activity of benzatropine is approximately one-half that of atropine, while its antihistamine activity approaches that of ]. Its anticholinergic effects have been established as therapeutically significant in the management of Parkinsonism. Benzatropine antagonizes the effect of ], decreasing the imbalance between the neurotransmitters acetylcholine and ], which may improve the symptoms of early Parkinson's disease.<ref>MIMS Australia Pty Ltd. MIMS.</ref>
			Benzatropine has been also identified, by a high throughput screening approach, as a potent differentiating agent for ]s, possibly working through ] and ] ]s. In preclinical models for multiple sclerosis, benzatropine decreased clinical symptoms and enhanced re-myelination.<ref name="pmid24107995">{{cite journal | vauthors = Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, Lairson LL | title = A regenerative approach to the treatment of multiple sclerosis | journal = Nature | volume = 502 | issue = 7471 | pages = 327–332 | date = October 2013 | pmid = 24107995 | pmc = 4431622 | doi = 10.1038/nature12647 | bibcode = 2013Natur.502..327D }}</ref>
	Benzatropine is a centrally acting ]/] agent resulting from the combination of the tropine portion of the ] molecule and the benzohydryl portion of ]. Animal studies have indicated that anticholinergic activity of benzatropine is approximately one-half that of atropine, while its antihistamine activity approaches that of ]. Its anticholinergic effects have been established as therapeutically significant in the management of parkinsonism. Benzatropine antagonises the effect of ], decreasing the imbalance between the neurotransmitters acetylcholine and ], which may improve the symptoms of early Parkinson's disease.<ref>MIMS Australia Pty Ltd. MIMS.</ref>
			==== Atypical dopamine reuptake inhibition ====
	==Chemistry==
			In addition to its anticholinergic activity, benztropine has been found to increase the availability of dopamine by blocking its ] and storage in central sites, and as a result, increasing ] activity. Benzatropine and ]s are atypical ],<ref name="pmid24194527 ">{{cite journal | vauthors = Hiranita T, Kohut SJ, Soto PL, Tanda G, Kopajtic TA, Katz JL | title = Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 348 | issue = 1 | pages = 174–191 | date = January 2014 | pmid = 24194527 | pmc = 3868882 | doi = 10.1124/jpet.113.208264 }}</ref> which might make them useful for people with ] secondary to antipsychotic therapy.<ref>{{cite journal | vauthors = Adler LA, Peselow E, Rosenthal M, Angrist B | title = A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis | journal = Psychopharmacology Bulletin | volume = 29 | issue = 2 | pages = 283–286 | year = 1993 | pmid = 8290678 }}</ref>
	Benztropine, 3-(diphenylmethoxy)tropane, is synthesized by the reaction of ] and diphenyldiazomethane.
	]
			==== Other actions ====
	*R.F. Phillips, N.J. Westfield, {{US Patent|2595405}} (1952).
			Benzatropine also acts as a ] (FIASMA).<ref name="pmid18504571">{{cite journal | vauthors = Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P | title = Identification of novel functional inhibitors of acid sphingomyelinase | journal = PLOS ONE | volume = 6 | issue = 8 | pages = e23852 | year = 2011 | pmid = 21909365 | pmc = 3166082 | doi = 10.1371/journal.pone.0023852 | doi-access = free | bibcode = 2011PLoSO...623852K }}</ref>
			==Other animals==
			In veterinary medicine, benzatropine is used to treat ] in stallions.<ref>{{cite journal | vauthors = Wilson DV, Nickels FA, Williams MA | title = Pharmacologic treatment of priapism in two horses | journal = Journal of the American Veterinary Medical Association | volume = 199 | issue = 9 | pages = 1183–1184 | date = November 1991 | doi = 10.2460/javma.1991.199.09.1183 | pmid = 1752772 }}</ref>
			==Naming==
			Since 1959, benz<u>a</u>tropine is the official ] of the medication under the INN scheme, the medication naming system coordinated by the ]; it is also the ] (BAN) given in the ],<ref name=INN/><ref name=MedNet/> and has been the official nonproprietary name in Australia since 2015.<ref name=TGA/> Regional variations of the "a" spelling are also used in French, Italian, Portuguese, and Spanish, as well as ] (all medications are assigned a Latin name by WHO).<ref name=MedNet/>
			"Benztropine" is the official ] (USAN), the medication naming system coordinated by the USAN Council, co-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA). It is also the ] (JAN)<ref name=KEGG>{{KEGG compound|D00778}}</ref> and was used in Australia until 2015, when it was harmonized with the INN.<ref name=TGA>{{cite web |url=https://www.tga.gov.au/updating-medicine-ingredient-names-list-affected-ingredients |title=Updating medicine ingredient names - list of affected ingredients |publisher=] |date=23 November 2015 |access-date=1 December 2020 |archive-date=27 November 2020 |archive-url=https://web.archive.org/web/20201127054118/https://www.tga.gov.au/updating-medicine-ingredient-names-list-affected-ingredients |url-status=live }}</ref>
			Both names may be modified to account for the ] salt as which the medication is formulated: the modified INN (INNm) and BAN (BANM) is ''benzatropine mesilate'', while the modified USAN is ''benztropine mesylate''.<ref name=Martindale>{{Cite book|editor=Sweetman, Sean C. |chapter=Antiparkinsonian Drugs |title=] |edition=36th |year=2009 |pages=797|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1}}</ref> The modified JAN is a hybrid form, ''benztropine mesilate''.<ref name=KEGG/>
			The misspelling benz<u>o</u>tropine is also occasionally seen in the literature.
	== References ==		== References ==
	{{Reflist|2}}		{{Reflist}}
	{{Antiparkinson}}		{{Antiparkinson}}
			{{Histamine receptor modulators}}
	{{Cholinergics}}
			{{Monoamine reuptake inhibitors}}
	{{Dopaminergics}}
			{{Muscarinic acetylcholine receptor modulators}}
	{{Histaminergics}}
			{{Portal bar | Medicine}}
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