Chemical structure of the TeCA mirtazapine. Notice its four rings fused together.

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced 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


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:

Never marketed

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


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[citation needed]. However, aside from mirtazapine, they do inhibit the reuptake of norepinephrine[citation needed]. TeCAs block the serotonin 5-HT2 receptors similarly to TCAs. Besides mirtazapine, they also block the α1-adrenergic receptor[citation needed]. 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[citation needed]. TeCAs block the histamine H1 receptor similarly to the TCAs, but tend to be even stronger antihistamines than TCAs[citation needed]. 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[citation needed]. Mianserin and mirtazapine are far less toxic than TCAs in overdose.[1][2]

Binding profiles

See also: Tricyclic antidepressant § Binding profiles

The binding profiles of various TeCAs in terms of their affinities (Ki, nM) for various receptors and transporters are as follows:[3]

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
Maprotiline 5,800 11–12 1,000 ND 51 ND 122 ND 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
Setiptiline >10,000 220 >10,000 ND ND ND ND ND ND ND ND 24 ND ND ND ND
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


  1. ^ Shaw, W. L. (1980-01-01). "The comparative safety of mianserin in overdose". Current Medical Research and Opinion. 6 (sup7): 44–51. doi:10.1185/03007998009114803. ISSN 0300-7995.
  2. ^ Waring, W. Stephen; Good, Alison M.; Bateman, D. Nicholas (2007-01-01). "Lack of significant toxicity after mirtazapine overdose: A five-year review of cases admitted to a regional toxicology unit". Clinical Toxicology. 45 (1): 45–50. doi:10.1080/15563650601005837. ISSN 1556-3650. PMID 17357381. S2CID 28546654.
  3. ^ 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.