Tetracyclic antidepressants (TeCAs) are a class of

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s that were first introduced in the 1970s. They are named after their

tetracyclic Tetracyclics are cyclic chemical compounds that contain four interconnected rings of atoms, e.g. Tröger's base. They have various pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or s ...

chemical structure, containing four rings of atoms, and are closely related to the

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and we ...

s (TCAs), which contain three rings of atoms.

List of TeCAs

Marketed

* Maprotiline (Ludiomil) – can also be classified as a TCA and grouped with the secondary amines *

Mianserin Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is close ...

(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) - an atypical antipsychotic sometimes used as an adjunct antidepressant

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 In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

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 Mazindol (brand names Mazanor, Sanorex) is a stimulant drug which is used as an appetite suppressant. It was developed by Sandoz Laboratories, Sandoz-Wander in the 1960s. Medical uses Mazindol is used in short-term (i.e., a few weeks) treatment ...

(Mazanor, Sanorex) – a monoamine reuptake inhibitor used as an appetite suppressant and with potential antidepressant effects, but not classified as a TeCA

Never marketed

* Aptazapine (CGS-7525A) – a close analogue of mirtazapine * Esmirtazapine (ORG-50,081) – the (''S'')-(+)

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of mirtazapine *

Oxaprotiline Oxaprotiline (developmental code name C 49-802 BDA), also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor of the tetracyclic antidepressant (TeCA) family that is related to maprotiline. Though investigated as an antidepressan ...

(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 Ciclazindol (WY-23409) is an antidepressant and anorectic drug of the tetracyclic chemical class that was developed in the mid to late 1970s, but was never marketed. It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a do ...

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

Pharmacology

TeCAs have diverse

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

and differ from TCAs in a number of ways. With the exception of amoxapine, TeCAs do not inhibit the reuptake of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

. However, aside from mirtazapine, they do inhibit the reuptake of norepinephrine. TeCAs block the

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

The binding profiles of various TeCAs in terms of their

affinities In post-classical history, an affinity was a collective name for the group ( retinue) of (usually) men whom a lord gathered around himself in his service; it has been described by one modern historian as "the servants, retainers, and other foll ...

(, ) for various receptors and

transporter Transporter may refer to: * Transporter (vehicles), types of vehicles designed to transport items * Transporter wagon, a railway car designed to carry another railway car * Volkswagen Transporter, a model of van * Transporter bridge, a bridge wh ...

s are as follows: The TeCAs act as antagonists or

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

s of the receptors and as

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s of the transporters.

References

{{Tricyclics Chemical classes of psychoactive drugs