Tetracyclic antidepressants (TeCAs) are a class ofantidepressants that were first introduced in the 1970s. They are named after theirtetracyclicchemical structure, containing fourrings of atoms, and are closely related to thetricyclic antidepressants (TCAs), which contain three rings of atoms.

• Maprotiline (Ludiomil) – can also be classified as a TCA and grouped with thesecondary amines
• Mianserin (Tolvon)
• Mirtazapine (Remeron)
• Setiptiline (Tecipul)

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
• Quetiapine (Seroquel) - anatypical antipsychotic sometimes used as an adjunct antidepressant

• Benzoctamine (Tacitin) – a tetracyclic compound and is closely related to maprotiline, with the two compounds differing only in the length of theirside chain, but benzoctamine is not used as an antidepressant and is instead used as ananxiolytic
• Loxapine (Adasuve, Loxitane) – atypical antipsychotic that produces amoxapine as a majormetabolite 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:

• Mazindol (Mazanor, Sanorex) – amonoamine reuptake inhibitor used as anappetite suppressant and with potential antidepressant effects, but not classified as a TeCA

• Aptazapine (CGS-7525A) – a closeanalogue of mirtazapine
• Esmirtazapine (ORG-50,081) – the (S)-(+)enantiomer of mirtazapine
• Oxaprotiline (C 49-802 BDA) – a close analogue of maprotiline

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

TeCAs have diversepharmacology and differ from TCAs in a number of ways. With the exception of amoxapine, TeCAs do notinhibit thereuptake ofserotonin^{[citation needed]}. However, aside from mirtazapine, they do inhibit the reuptake ofnorepinephrine^{[citation needed]}. TeCAs block theserotonin5-HT₂ receptors similarly to TCAs. Besides mirtazapine, they also block theα₁-adrenergic receptor^{[citation needed]}. Conversely, whereas TCAs have relatively lowaffinity for theα₂-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 thehistamineH₁ receptor similarly to the TCAs, but tend to be even strongerantihistamines than TCAs^{[citation needed]}. On the other hand, in contrast to almost all TCAs, TeCAs have only low affinity for themuscarinic acetylcholine receptors, and for this reason, are associated with few or noanticholinergicside effects^{[citation needed]}. Mianserin and mirtazapine are far lesstoxic than TCAs inoverdose.^[1][2]

The binding profiles of various TeCAs in terms of theiraffinities (K_i,nM) for variousreceptors andtransporters are as follows:^[3]

The TeCAs act asantagonists orinverse agonists of the receptors and asinhibitors of the transporters.

• List of antidepressants
• Noradrenergic and specific serotonergic antidepressant

• Chemical classes of psychoactive drugs
• Tetracyclic antidepressants

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