Clorotepine (; brand names Clotepin, Clopiben), also known as octoclothepin or octoclothepine, is an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

of the

tricyclic Tricyclics are chemical compounds that contain three interconnected rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. Among these are antid ...

group which was derived from

perathiepin Perathiepin is a neuroleptic drug of the tricyclic family which was developed in the 1960s but was never marketed. In animal studies it was found to possess central depressant, antihistamine, antiserotonergic, and analgesic effects. See also ...

in 1965 and marketed in the

Czech Republic The Czech Republic, or simply Czechia, is a landlocked country in Central Europe. Historically known as Bohemia, it is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the southeast. The ...

by Spofa in or around 1971 for the treatment of

schizophrenic Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

. Clorotepine is known to have high

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 Partn ...

for the

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

D₁, D₂, D₃, and D₄ receptors, the

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 ...

5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆, and 5-HT₇ receptors, the α_1A-, α_1B-, and α_1D-adrenergic receptors, and 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 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, where it has been it has been confirmed to act as an

antagonist 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 ...

(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 ...

) at most sites (and likely is as such at all of them based on structure–activity relationships), and it also blocks 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 ...

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'', ...

via

inhibition 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 ...

of the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

. Due to its very potent activity at the D₂ receptor, along with tefludazine, clorotepine was used as the basis for developing a

3-dimensional Three-dimensional space (also: 3D space, 3-space or, rarely, tri-dimensional space) is a geometric setting in which three values (called ''parameters'') are required to determine the position of an element (i.e., point). This is the informal ...

(3D)

pharmacophore 300px, An example of a pharmacophore model. A pharmacophore is an abstract description of molecular features that are necessary for molecular recognition of a ligand by a biological macromolecule. IUPAC defines a pharmacophore to be "an ensemble o ...

for D₂ receptor antagonists.

References

{{Tricyclics Antipsychotics Chloroarenes Dibenzothiepines Diphenylethylpiperazines Sedatives