Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...

, containing four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

List of TeCAs

Marketed

Maprotiline Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary am ...

(Ludiomil) – can also be classified as a TCA and grouped with the

secondary amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...

s * Mianserin (Tolvon) * Mirtazapine (Remeron) * Setiptiline (Tecipul) Drugs that contain four rings not all fused together but are sometimes still classified as TeCAs include: *

Amoxapine Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 ...

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

Quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

(Seroquel) - an

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

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 In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a ...

, but benzoctamine is not used as an antidepressant and is instead used as an

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

Loxapine Loxapine, sold under the brand names Loxitane and Adasuve (''inhalation'' only) among others, is an antipsychotic medication used primarily in the treatment of schizophrenia. The medicine is a member of the dibenzoxazepine class and structural ...

(Adasuve, Loxitane) – a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

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: * Mazindol (Mazanor, Sanorex) – a monoamine reuptake inhibitor used as an

appetite suppressant An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" ...

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 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

Pharmacology

TeCAs have diverse pharmacology and differ from TCAs in a number of ways. With the exception of amoxapine, TeCAs do not

inhibit 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 neurotr ...

the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

of serotonin. However, aside from mirtazapine, they do inhibit the reuptake of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

. 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

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...

s 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 Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s. Mianserin and mirtazapine are far less

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

than TCAs in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

Binding profiles

The binding profiles of various TeCAs in terms of their affinities (, ) for various receptors and transporters are as follows: The TeCAs act as antagonists or inverse agonists of the receptors and as inhibitors of the transporters.

References

{{Tricyclics Chemical classes of psychoactive drugs