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 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 wer ...

s (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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...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 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 closely ...

(Tolvon) *

Mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an Atypical antidepressant, atypical antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks, but can also man ...

(Remeron) *

Setiptiline Setiptiline (brand name Tecipul), also known as teciptiline, is a tetracyclic antidepressant (TeCA) that acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). It was launched in 1989 for the treatment of depression in Japan ...

(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 Benzoctamine is a drug that possesses sedative and anxiolytic properties. Marketed as Tacitin by Ciba-Geigy, it is different from most sedative drugs because in most clinical trials it does not produce respiratory depression, but actually sti ...

(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 l ...

, 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 anxi ...

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 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 A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine ...

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 ...

and with potential antidepressant effects, but not classified as a TeCA

Never marketed

Aptazapine Aptazapine (developmental code name CGS-7525A) is a tetracyclic antidepressant (TeCA) that was assayed in clinical trials for the treatment of depression in the 1980s but was never marketed. It is a potent α2-adrenergic receptor antagonist w ...

(CGS-7525A) – a close analogue of mirtazapine *

Esmirtazapine Esmirtazapine (ORG-50,081) is a drug which was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause. Esmirtazapine is the (''S'')-(+)- enantiomer of mirtazapine and poss ...

(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 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 pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...

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 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

5-HT₂ receptors similarly to TCAs. Besides mirtazapine, they also block the α₁-adrenergic receptor. Conversely, whereas TCAs have relatively low

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

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 Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

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 receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

s, 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 system ...

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 subst ...

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

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

s and transporters are as follows: The TeCAs act as

antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

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 inhibitors of the transporters.

References

{{Tricyclics Chemical classes of psychoactive drugs