5-HT2C receptor

5-hydroxytryptamine (serotonin) receptor 2C, also known as HTR2C, is a 5-HT2 receptor, but also denotes the human gene encoding it.

Function

 * CNS: anxiety, choroid plexus: cerebrospinal fluid (CSF) secretion

Ligands
Numerous (ex-)prescription, illicit and research drugs contain a 5-HT2C component in their binding profile, including fluoxetine, mianserin, clozapine, agomelatine, dextro-norfenfluramine, psilocin, DOI, α-methyl-serotonin, MK-212, m-CPP, FG-7142, Ro60-0175, mesulergine, metergoline, ritanserin, methiothepin, 5-methoxygramine, and many more. Some compounds with a more pronounced selectivity for the 5-HT2C receptor subtype are listed below. Note, that in the following context the term "functional selectivity" does not refer to differentiation of transductional pathways.

Agonists

 * YM348: potent, full agonist, high affinity, high functional selectivity, orally active


 * (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine: potent, full agonist with an outstanding selectivity profile


 * (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one: agonist, >300-fold functional selectivity over 5-HT2B and >70-fold over 5-HT2A


 * Lorcaserin: full agonist, fair selectivity profile

Antagonists

 * FR260010: silent antagonist, high affinity, selective over 5-HT2A and many other receptors; orally active.


 * RS-102221: silent antagonist, 100-fold selectivity compared to the 5-HT2A and -HT2B receptor subtypes

Mixed response
A more extensive examination on signal transduction was carried out for
 * SB-243213: high affinity, >100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and ion channels; long duration of action in vivo (>8 h); anxiolytic-like effects. Inverse agonist for the PLA2 response, for GTPgammaS binding, for reduction of constitutive desensitization, and for enhancement of dopamine release in the rat nucleus accumbens. Silent antagonist for the PLC cascade. (See also functional selectivity).

Receptor regulation
Agonists promote 5-HT2C receptor internalization leading to tachyphylaxis.