Tetracyclic antidepressant

Not to be confused with Tetracycline.

Skeletal formula of tetracyclic antidepressant mirtazapine. Note its four fused "rings".

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

List of TeCAs

The TeCAs include the following agents:

• Marketed
  • Maprotiline (Deprilept, Ludiomil, Psymion)
  • Mianserin (Bolvidon, Norval, Tolvon)
  • Mirtazapine (Remeron, Avanza, Zispin)
  • Pirlindole (Pirazidol) — a tetracyclic reversible inhibitor of monoamine oxidase A (RIMA) used in Russia
  • Setiptiline (Tecipul)
• Not marketed
  • Aptazapine (CGS-7525A)
  • Metralindole — a tetracyclic RIMA investigated as an antidepressant
  • Esmirtazapine (ORG-50,081)
  • Oxaprotiline (C 49-802 BDA)
• Doubtful classification
  • Amoxapine (Asendin) — contains four, but not fused together rings; widely classified as a secondary amine tricyclic antidepressant
  • Ciclazindol (WY-23,409)
  • Loxapine (Loxapac, Loxitane, Adasuve) — a tricyclic antipsychotic with antidepressant properties; produces amoxapine as an active metabolite
  • Mazindol (Mazanor, Sanorex)

Pharmacology

Binding profiles

The affinities (K_d (nM)) of a selection of TeCAs have been compared below at an assortment of binding sites:

Compound	SERT	NET	DAT	5-HT1A	5-HT2A	α1	α2	D2	H1	mACh
Amoxapine	58	16.0	4,310	220	0.6	50	2,600	160	25	1,000
Loxapine	2,400	380	9,000	2,900	1.7	28	2,400	70	4.9	450
Maprotiline	5,800	11.1	1,000	12,000	120	91	9,400	350	2.0	560
Mianserin	4,000	101	9,400	190	4.3	74	4.3	2,197	1.7	820
Mirtazapine	>100,000	1,640	>100,000	?	69	500	19	>5,454	0.1	670
Oxaprotiline	3,900	4.9	4,340	67,000	2,400	620	42,000	?	21	2,900

The selected ligands act as antagonists (or inverse agonists depending on the site in question) at all receptors listed and as inhibitors of all transporters listed.