5-HT2B receptor

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a is_associated_with::protein that in humans is encoded by the HTR2B is_associated_with::gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the is_associated_with::neurotransmitter is_associated_with::serotonin (5-hydroxytryptamine, 5-HT).

Function
The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of is_associated_with::serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of is_associated_with::hallucinogenic is_associated_with::substituted amphetamines.

The 5-HT2B receptor subtype is involved in:
 * CNS: is_associated_with::presynaptic inhibition, behavioural effects
 * Vascular: pulmonary is_associated_with::vasoconstriction
 * Cardiac: The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice. The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts, which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.


 * is_associated_with::Serotonin transporter: 5-HT2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma, and with the abnormal acute serotonin release produced by drugs such as is_associated_with::MDMA. Surprisingly however 5-HT2B receptor activation appears to be protective against the development of is_associated_with::serotonin syndrome following elevated extracellular serotonin levels, despite its role in modulating serotonin release.

Clinical significance
5-HT2B receptors have also been strongly implicated in drug-induced is_associated_with::valvular heart disease. In this context, it is generally considered to be an is_associated_with::antitarget.

The structure of the 5-HT2B receptor was recently solved in complex with the valvulopathogenic drug is_associated_with::ergotamine.

Ligands
As of 2009, few highly selective 5-HT2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT2C binding. Research in this area has been limited due to the cardiotoxicity of 5-HT2B agonists, and the lack of clear therapeutic application for 5-HT2B antagonists, but there is still a need for selective ligands for scientific research.

Agonists

 * Selective
 * is_associated_with::BW-723C86: fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo.
 * is_associated_with::Ro60-0175 functionally selective over 5-HT2A, potent agonist at both 5-HT2B/C
 * is_associated_with::VER-3323: selective for 5-HT2B/C over 5-HT2A
 * is_associated_with::α-Methyl-5-HT - moderately selective over 5-HT2A/C
 * is_associated_with::6-APB
 * is_associated_with::psilocin - 23x greater selectivity for human cloned 5-HT2B receptors over 5-HT2A.


 * Non-selective
 * is_associated_with::Guanfacine - an α2A agonist, but has 5-HT2B agonistic activity at therapeutic concentrations.
 * is_associated_with::MDMA (Ecstasy)
 * MDA
 * MEM
 * is_associated_with::Pergolide
 * is_associated_with::Cabergoline
 * is_associated_with::Norfenfluramine
 * is_associated_with::Chlorphentermine
 * is_associated_with::Aminorex
 * mCPP
 * is_associated_with::Bromo-dragonfly
 * DMT
 * is_associated_with::5-MeO-DMT
 * LSD-25 - About equal affinty for human cloned 5-HT2B and 5-HT2A receptors.

Antagonists

 * is_associated_with::Agomelatine - primarily a is_associated_with::melatonin Mt1/Mt2 receptor agonist, with a less potent antagonism of 5-HT2B and 5-HT2C.
 * is_associated_with::Sarpogrelate: a mixed 5-HT2A/B antagonist
 * is_associated_with::Lisuride: a is_associated_with::dopamine agonist of the is_associated_with::ergoline class, that is also a 5-HT2B antagonist and a dual 5-HT2A/C agonist
 * is_associated_with::Tegaserod: primarily a 5-HT4 agonist, but also a 5-HT2B antagonist
 * is_associated_with::RS-127,445: high affinity; subtype selective (1000x), selective over at least eight other 5-HTR types; orally bioavailable.
 * is_associated_with::SDZ SER-082: a mixed 5-HT2B/C antagonist
 * EGIS-7625: high selectivity over 5-HT2A
 * is_associated_with::PRX-08066
 * SB-200,646
 * is_associated_with::SB-204,741
 * is_associated_with::SB-206,553: mixed 5-HT2B/C antagonist and PAM at α7 nAChR
 * is_associated_with::SB-215,505
 * SB-228,357
 * is_associated_with::LY-266,097
 * is_associated_with::LY-272,015

Possible applications
5-HT2B antagonists have previously been proposed as treatment for is_associated_with::migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued. More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic is_associated_with::heart disease. Research claims serotonin 5-HT2B receptors have effect on liver regeneration.