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, ORG-37684, 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

 * A-372,159: partial agonist, Ki 3nM, 100x selectivity over 5-HT2B


 * Lorcaserin: full agonist, fair selectivity profile


 * MK-212


 * Ro60-0175


 * WAY-629


 * WAY-161,503


 * YM-348: 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

Antagonists

 * FR-260,010: high affinity, selective over 5-HT2A and many other receptors; orally active.


 * RS-102,221: 100-fold selectivity compared to the 5-HT2A and -HT2B receptor subtypes


 * SB-200,646: mixed 5-HT2B/2C antagonist


 * SB-206,553: mixed 5-HT2B/2C antagonist


 * SB-221,284: mixed 5-HT2B/2C antagonist


 * SB-242,084


 * compound 15k: IC50 = 0.5 nM; >2000x selective over 5-HT1A, -2A, and -6, and dopamine D2–D4 receptors

Inverse agonists

 * SB-228,357: mixed 5-HT2C inverse agonist / 5-HT2B antagonist

Mixed response

 * SB-243,213: 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).