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{{See also|Tricyclic antidepressant#Binding profiles}} {{See also|Tricyclic antidepressant#Binding profiles}}


The binding profiles of various TeCAs and some ]s 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 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | accessdate = 14 August 2017 | url = https://pdsp.unc.edu/databases/kidb.php}}</ref>
The ] (K<sub>i</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>


{| class="wikitable sortable" {| class="wikitable" style="font-size: 80%; text-align: center;"
|+
! '''Compound''' || '''{{abbrlink|SERT|Serotonin transporter}}''' || '''{{abbrlink|NET|Norepinephrine transporter}}''' || '''{{abbrlink|DAT|Dopamine transporter}}''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || ''']''' || '''{{abbrlink|mACh|Muscarinic acetylcholine receptor}}''' ! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !! ] !!] !! ] !! {{abbrlink|mACh|Muscarinic acetylcholine receptor}}
|- |-
| ] || 58 || 16.0 || 4,310 || 220 || 0.6 || 50 || 2,600 || 160 || 25 || 1,000
| ] || 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
<!-- |-
⚫ |-
| ] || 2,400 || 380 || 9,000 || 2,900 || 1.7 || 28 || 2,400 || 70 || 4.9 || 450--><!--Technically not a TeCA-->
| ] || >10,000 || 5,700 || >10,000 || 2,460 || 6.6 || {{abbr|ND|No data}} || 13 || {{abbr|ND|No data}} || 31 || 88 || 31–53 || 80–151 || 11 || 2.2–4.9 || 208 || 120–1,270
⚫ |-
⚫ |-
| ] || 5,800 || 11.1 || 1,000 || 12,000 || 120 || 91 || 9,400 || 350 || 2.0 || 560
| ] || 5,800 || 11–12 || 1,000 || {{abbr|ND|No data}} || 51 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || 122 || {{abbr|ND|No data}} || 50 || 90 || 9,400 || 350–665 || 0.79–2.0 || 776 || 570
⚫ |-
⚫ |-
| ] || 4,000 || 101 || 9,400 || 190 || 4.3 || 74 || 4.3 || 2,197 || 1.7 || 820
| ] || 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
⚫ |-
|-
| ] || >10,000 || ≥4,600 || >10,000 || >1,000 || 69 || 500 || 19 || >5,454 || 0.1 || 670 | ] || >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
<!-- |-
|- class="sortbottom"
| ] || 3,900 || 4.9 || 4,340 || 67,000 || 2,400 || 620 || 42,000 || ? || 21 || 2,900--><!-- Never marketed-->
| 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.
|} |}


The selected ligands act as ] (or ]s depending on the site in question) at all ] listed and as ] of all ] listed. The TeCAs act as ] or ]s of the receptors and as ]s of the transporters.


==See also== ==See also==

Revision as of 10:21, 8 September 2017

Not to be confused with Tetracycline.
Chemical structure of the TeCA mirtazapine. Notice its four rings fused together.

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced starting in the 1970s. They are named after their tetracyclic chemical structure, containing four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

List of TeCAs

Marketed

Drugs that contain four rings not all fused together but are sometimes still classified as TeCAs include:

  • Amoxapine (Asendin) – often classified as a TCA and grouped with the secondary amines

Miscellaneous

  • Benzoctamine (Tacitin) – a tetracyclic compound and is closely related to maprotiline, with the two compounds differing only in the length of their side chain, but benzoctamine is not used as an antidepressant and is instead used as an anxiolytic
  • Loxapine (Adasuve, Loxitane) – a typical antipsychotic that produces amoxapine as a major metabolite and is said to have antidepressant effects, but it is not usually regarded as a TeCA

Drugs that contain four rings not all fused together but could still be classified as tetracyclic include:

Never marketed

Drugs that contain four rings not all fused together but could still be classified as tetracyclic include:

  • Ciclazindol (WY-23,409) – a close analogue of mazindol

Pharmacology

See also: Pharmacology of antidepressants

TeCAs have diverse pharmacology and differ from TCAs in a number of ways. With the exception of amoxapine, TeCAs do not inhibit the reuptake of serotonin. However, aside from mirtazapine, they do inhibit the reuptake of norepinephrine. TeCAs block the serotonin 5-HT2 receptors similarly to TCAs. Besides mirtazapine, they also block the α1-adrenergic receptor. Conversely, whereas TCAs have relatively low affinity for the α2-adrenergic receptor, mianserin and mirtazapine potently antagonize this receptor, and this action is thought to be involved in their antidepressant effects. TeCAs block the histamine H1 receptor similarly to the TCAs, but tend to be even stronger antihistamines than TCAs. On the other hand, in contrast to almost all TCAs, TeCAs have only low affinity for the muscarinic acetylcholine receptors, and for this reason, are associated with few or no anticholinergic side effects. Mianserin and mirtazapine are far less toxic than TCAs in overdose.

Binding profiles

See also: Tricyclic antidepressant § Binding profiles

The binding profiles of various TeCAs and some metabolites in terms of their affinities (Ki, nM) for various receptors and transporters are as follows:

Compound SERTTooltip Serotonin transporter NETTooltip Norepinephrine transporter DATTooltip Dopamine transporter 5-HT1A 5-HT2A 5-HT2B 5-HT2C 5-HT3 5-HT6 5-HT7 α1 α2 D2 H1 H2 mAChTooltip Muscarinic acetylcholine receptor
Amoxapine 58 16 4,310 ND 0.5 ND 2.0 ND 6.0–50 41 50 2,600 3.6–160 7.9–25 ND 1,000
Loxapine >10,000 5,700 >10,000 2,460 6.6 ND 13 ND 31 88 31–53 80–151 11 2.2–4.9 208 120–1,270
Maprotiline 5,800 11–12 1,000 ND 51 ND ND 122 ND 50 90 9,400 350–665 0.79–2.0 776 570
Mianserin 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
Mirtazapine >10,000 ≥4,600 >10,000 ≥3,330 6.3–69 200 8.9–39 7.9 ND 265 316–1,815 18–88 >5,454 0.14–1.6 >10,000 670
Values are Ki (nM). 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.

The TeCAs act as antagonists or inverse agonists of the receptors and as inhibitors of the transporters.

See also

References

  1. Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
Antidepressants (N06A)
Specific reuptake inhibitors and/or receptor modulators
SSRIsTooltip Selective serotonin reuptake inhibitors
SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors
NRIsTooltip Norepinephrine reuptake inhibitors
NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors
NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants
SARIsTooltip Serotonin antagonist and reuptake inhibitors
SMSTooltip Serotonin modulator and stimulators
Others
Tricyclic and tetracyclic antidepressants
TCAsTooltip Tricyclic antidepressants
TeCAsTooltip Tetracyclic antidepressants
Others
Monoamine oxidase inhibitors
Non-selective
MAOATooltip Monoamine oxidase A-selective
MAOBTooltip Monoamine oxidase B-selective
Adjunctive therapies
Miscellaneous
Pharmacodynamics
Adrenergic receptor modulators
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
Dopamine receptor modulators
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
Histamine receptor modulators
H1
Agonists
Antagonists
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
See also
Receptor/signaling modulators
Monoamine metabolism modulators
Monoamine reuptake inhibitors
Monoamine reuptake inhibitors
DATTooltip Dopamine transporter
(DRIsTooltip Dopamine reuptake inhibitors)
NETTooltip Norepinephrine transporter
(NRIsTooltip Norepinephrine reuptake inhibitors)
SERTTooltip Serotonin transporter
(SRIsTooltip Serotonin reuptake inhibitors)
VMATsTooltip Vesicular monoamine transporters
Others
See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins
Muscarinic acetylcholine receptor modulators
mAChRsTooltip Muscarinic acetylcholine receptors
Agonists
Antagonists
Precursors
(and prodrugs)
See also
Receptor/signaling modulators
Nicotinic acetylcholine receptor modulators
Acetylcholine metabolism/transport modulators
Serotonin receptor modulators
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Tricyclics
Classes
Antidepressants
(Tricyclic antidepressants (TCAs))
Antihistamines
Antipsychotics
Anticonvulsants
Anticholinergics
Others
Categories: