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{{Short description|Class of pharmaceutical drugs}} |
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{{Distinguish|Tetracycline}} |
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{{Distinguish|Tetracycline|Tricyclic antidepressant}} |
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{{Refimprove|date=November 2013}} |
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] of tetracyclic antidepressant ]. Note its '''four fused''' ].]] |
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] of the TeCA ]. Notice its four ] fused together.]] |
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'''Tetracyclic antidepressants''' ('''TeCAs''') are a class of ]s that were first introduced in the 1970s. They are named after their ], which contains four ], and are closely related to the ]s (TCAs), which contain three rings of atoms. |
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'''Tetracyclic antidepressants''' ('''TeCAs''') are a class of ]s that were first introduced in the 1970s. They are named after their ] ], containing four ], and are closely related to the ]s (TCAs), which contain three rings of atoms. |
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== List of TeCAs == |
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==List of TeCAs== |
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The TeCAs include: |
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* Marketed |
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===Marketed=== |
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** ] (Deprilept, Ludiomil, Psymion) |
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* ] (Ludiomil) – can also be classified as a TCA and grouped with the ]s |
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** ] (Bolvidon, Norval, Tolvon) |
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* ] (Tolvon) |
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** ] (Remeron, Avanza, Zispin) |
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* ] (Remeron) |
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** ] (Tecipul) |
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* ] (Tecipul) |
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* Never marketed |
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** ] (CGS-7525A) |
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** ] (ORG-50,081) |
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** ] (C 49-802 BDA) |
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Drugs that contain four rings not fused together but are sometimes classified as TeCAs include: |
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Drugs that contain four rings not all fused together but are sometimes still classified as TeCAs include: |
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* ] (Asendin) – often classified as a TCA and grouped with the secondary amines |
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* Marketed |
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** ] (Asendin) — often classified as a secondary amine tricyclic antidepressant |
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* ] (Seroquel) - an ] sometimes used as an adjunct antidepressant |
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** ] (Loxapac, Loxitane, Adasuve) — a tricyclic ] with antidepressant properties; produces amoxapine as an ] |
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** ] (Mazanor, Sanorex) |
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* Never marketed |
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** ] (WY-23,409) |
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====Miscellaneous==== |
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] (Tacitin) is closely related to the TeCAs and particularly to maprotiline, with the two compounds differing only in the length of their ], but benzoctamine is not used as an antidepressant and is instead used as an ]. |
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* ] (Tacitin) – a tetracyclic compound and is closely related to maprotiline, with the two compounds differing only in the length of their ], but benzoctamine is not used as an antidepressant and is instead used as an ] |
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* ] (Adasuve, Loxitane) – a ] that produces amoxapine as a major ] and is said to have antidepressant effects, but it is not usually regarded as a TeCA |
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Drugs that contain four rings not all fused together but could still be classified as tetracyclic include: |
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== Pharmacology == |
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* ] (Mazanor, Sanorex) – a ] used as an ] and with potential antidepressant effects, but not classified as a TeCA |
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=== Binding profiles === |
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The ] (K<sub>d</sub> (nM)) of a selection of TeCAs have been compared below at an assortment of ]s:<ref name=Goodman>{{cite book|last=Brunton|first=Laurence|title=Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th Edition|year=2011|publisher=McGraw-Hill|location=China|isbn=978-0-07-162442-8|pages=406–410}}</ref><ref name="pmid9537821">{{cite journal |vauthors=Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–258 |date=December 1997 | pmid = 9537821 | doi = 10.1016/S0014-2999(97)01393-9| url = http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)01393-9}}</ref><ref name="pmid3816971">{{cite journal |vauthors=Wander TJ, Nelson A, Okazaki H, Richelson E | title = Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro | journal = European Journal of Pharmacology | volume = 132 | issue = 2–3 | pages = 115–121 |date=December 1986 | pmid = 3816971 | doi = 10.1016/0014-2999(86)90596-0| url = }}</ref><ref name="pmid6086881">{{cite journal |vauthors=Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 230 | issue = 1 | pages = 94–102 |date=July 1984 | pmid = 6086881 | doi = | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6086881}}</ref><ref name="pmid10193665">{{cite journal |vauthors=Tatsumi M, Jansen K, Blakely RD, Richelson E | title = Pharmacological profile of neuroleptics at human monoamine transporters | journal = European Journal of Pharmacology | volume = 368 | issue = 2–3 | pages = 277–283 |date=March 1999 | pmid = 10193665 | doi = 10.1016/S0014-2999(99)00005-9| url = }}</ref><ref name="pmid2891550">{{cite journal |vauthors=Wander TJ, Nelson A, Okazaki H, Richelson E | title = Antagonism by neuroleptics of serotonin 5-HT1A and 5-HT2 receptors of normal human brain in vitro | journal = European Journal of Pharmacology | volume = 143 | issue = 2 | pages = 279–282 |date=November 1987 | pmid = 2891550 | doi = 10.1016/0014-2999(87)90544-9| url = http://linkinghub.elsevier.com/retrieve/pii/0014-2999(87)90544-9}}</ref><ref name="pmid6149136">{{cite journal |vauthors=Richelson E, Nelson A | title = Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro | journal = European Journal of Pharmacology | volume = 103 | issue = 3–4 | pages = 197–204 |date=August 1984 | pmid = 6149136 | doi = 10.1016/0014-2999(84)90478-3| url = }}</ref><ref name="pmid15771415">{{cite journal |vauthors=Fernández J, Alonso JM, Andrés JI, etal | title = Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 6 | pages = 1709–12 |date=March 2005 | pmid = 15771415 | doi = 10.1021/jm049632c}}</ref><ref name="pmid3419539">{{cite journal |vauthors=de Boer TH, Maura G, Raiteri M, de Vos CJ, Wieringa J, Pinder RM | title = Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers | journal = Neuropharmacology | volume = 27 | issue = 4 | pages = 399–408 |date=April 1988 | pmid = 3419539 | doi = 10.1016/0028-3908(88)90149-9| url = }}</ref> |
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===Never marketed=== |
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* ] (CGS-7525A) – a close ] of mirtazapine |
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| '''Compound''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' |
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* ] (ORG-50,081) – the (''S'')-(+) ] of mirtazapine |
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* ] (C 49-802 BDA) – a close analogue of maprotiline |
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| ] || 58 || 16.0 || 4,310 || 220 || 0.6 || 50 || 2,600 || 160 || 25 || 1,000 |
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Drugs that contain four rings not all fused together but could still be classified as tetracyclic include: |
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| ] || 2,400 || 380 || 9,000 || 2,900 || 1.7 || 28 || 2,400 || 70 || 4.9 || 450 |
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* ] (WY-23,409) – a close analogue of mazindol |
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| ] || 5,800 || 11.1 || 1,000 || 12,000 || 120 || 91 || 9,400 || 350 || 2.0 || 560 |
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==Pharmacology== |
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| ] || 4,000 || 101 || 9,400 || 190 || 4.3 || 74 || 4.3 || 2,197 || 1.7 || 820 |
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{{See also|Pharmacology of antidepressants}} |
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| ] || >100,000 || 1,640 || >100,000 || ? || 69 || 500 || 19 || >5,454 || 0.1 || 670 |
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TeCAs have diverse ] and differ from TCAs in a number of ways. With the exception of amoxapine, TeCAs do not ] the ] of ]{{Citation needed|date=July 2020}}. However, aside from mirtazapine, they do inhibit the reuptake of ]{{Citation needed|date=July 2020}}. TeCAs block the ] ]s similarly to TCAs. Besides mirtazapine, they also block the ]{{Citation needed|date=July 2020}}. Conversely, whereas TCAs have relatively low ] for the ], mianserin and mirtazapine potently antagonize this receptor, and this action is thought to be involved in their antidepressant effects{{Citation needed|date=July 2020}}. TeCAs block the ] ] similarly to the TCAs, but tend to be even stronger ]s than TCAs{{Citation needed|date=July 2020}}. On the other hand, in contrast to almost all TCAs, TeCAs have only low affinity for the ]s, and for this reason, are associated with few or no ] ]s{{Citation needed|date=July 2020}}. Mianserin and mirtazapine are far less ] than TCAs in ].<ref>{{Cite journal|last=Shaw|first=W. L.|date=1980-01-01|title=The comparative safety of mianserin in overdose|url=https://doi.org/10.1185/03007998009114803|journal=Current Medical Research and Opinion|volume=6|issue=sup7|pages=44–51|doi=10.1185/03007998009114803|issn=0300-7995}}</ref><ref>{{Cite journal|last1=Waring|first1=W. Stephen|last2=Good|first2=Alison M.|last3=Bateman|first3=D. Nicholas|date=2007-01-01|title=Lack of significant toxicity after mirtazapine overdose: A five-year review of cases admitted to a regional toxicology unit|url=https://doi.org/10.1080/15563650601005837|journal=Clinical Toxicology|volume=45|issue=1|pages=45–50|doi=10.1080/15563650601005837|pmid=17357381 |s2cid=28546654 |issn=1556-3650}}</ref> |
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| ] || 3,900 || 4.9 || 4,340 || 67,000 || 2,400 || 620 || 42,000 || ? || 21 || 2,900 |
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===Binding profiles=== |
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{{See also|Tricyclic antidepressant#Binding profiles}} |
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The binding profiles of various TeCAs in terms of their ] ({{abbr|K<sub>i</sub>|inhibitory constant}}, {{abbr|nM|nanomolar}}) for various ]s and ]s are as follows:<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | author1 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/kidb.php}}</ref> |
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{| class="wikitable sortable" style="font-size: 80%; text-align: center;" |
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|+ |
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! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !!] !! ] !! {{abbrlink|mACh|Muscarinic acetylcholine receptor}} |
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| ] || 58 || 16 || 4,310 || {{abbr|ND|No data}} || 0.5 || {{abbr|ND|No data}} || 2.0 || {{abbr|ND|No data}} || 6.0–50 || 41 || 50 || 2,600 || 3.6–160 || 7.9–25 || {{abbr|ND|No data}} || 1,000 |
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| ] || 5,800 || 11–12 || 1,000 || {{abbr|ND|No data}} || 51 || {{abbr|ND|No data}} || 122 || ND ||{{abbr|ND|No data}} || 50 || 90 || 9,400 || 350–665 || 0.79–2.0 || 776 || 570 |
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| ] || 4,000 || 71 || 9,400 || 400–2,600 || 1.6–20 || 1.6–55 || 0.63–6.5 || 5.8–300 || 55–81 || 48–56 || 34 || 3.8–73 || ≥2,100 || 0.30–1.7 || 437 || 820 |
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| ] || >10,000 || ≥4,600 || >10,000 || ≥3,330 || 6.3–69 || 200 || 8.9–39 || 7.9 || {{abbr|ND|No data}} || 265 || 316–1,815 || 18–88 || >5,454 || 0.14–1.6 || >10,000 || 670 |
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| ] || >10,000 || 220 || >10,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || 24 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} |
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| colspan="17" | Values are {{abbr|K<sub>i</sub>|inhibitory constant}} ({{abbr|nM|nanomolar}}). The smaller the value, the more strongly the drug binds to the site. For assay species and references, see the individual drug articles. Most but not all values are for human proteins. |
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The selected ligands act as ] (or ]s depending on the site in question) at all ] listed and as ] of all ] listed. |
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The TeCAs act as ] or ]s of the receptors and as ]s of the transporters. |
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==See also== |
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==See also== |
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* ] |
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*] |
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*] |
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* ] |
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== References == |
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==References== |
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{{Reflist|2}} |
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{{Reflist|2}} |
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{{Antidepressants}} |
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{{Antidepressants}} |
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{{Navboxes |
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{{Acetylcholine receptor modulators}} |
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| title = ] |
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{{Adrenergic receptor modulators}} |
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{{Adrenergic receptor modulators}} |
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{{Dopamine receptor modulators}} |
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{{Dopamine receptor modulators}} |
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{{Histamine receptor modulators}} |
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{{Histamine receptor modulators}} |
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{{Monoamine reuptake inhibitors}} |
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{{Monoamine reuptake inhibitors}} |
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{{Muscarinic acetylcholine receptor modulators}} |
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{{Serotonin receptor modulators}} |
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{{Serotonin receptor modulators}} |
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{{Tricyclics}} |
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{{Tetracyclics}} |
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] |
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Drugs that contain four rings not all fused together but are sometimes still classified as TeCAs include:
Drugs that contain four rings not all fused together but could still be classified as tetracyclic include:
Drugs that contain four rings not all fused together but could still be classified as tetracyclic include:
