5-HT2B receptor
Encyclopedia
5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor
, but also denotes the human gene
encoding it.
. 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 phenylisopropylamine
hallucinogens.
The 5-HT2B receptor subtype is involved in:
Non-selective
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 heart disease
.
5-HT2 receptor
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...
, but also denotes the human gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
encoding it.
Function
The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
. 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 phenylisopropylamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
hallucinogens.
The 5-HT2B receptor subtype is involved in:
- CNS: presynaptic inhibition, behavioural effects
- Vascular: pulmonary vasoconstrictionVasoconstrictionVasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
- 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.
- Serotonin transporterSerotonin transporterThe serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
: 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 MDMA. Surprisingly however 5-HT2B receptor activation appears to be protective against the development of serotonin syndromeSerotonin syndromeSerotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
following elevated extracellular serotonin levels, despite its role in modulating serotonin release.
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 5HT2B agonists, and the lack of clear therapeutic application for 5HT2B antagonists, but there is still a need for selective ligands for scientific research.Agonists
Selective- BW-723C86BW-723C86BW-723C86 is a tryptamine derivative drug which acts as a 5-HT2B receptor agonist. It has anxiolytic effects in animal studies, and is also used for investigating the function of the 5-HT2B receptor in a range of other tissues....
: fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo. - Ro60-0175Ro60-0175Ro60-0175 is a drug developed by Hoffmann–La Roche, which has applications in scientific research. It acts as a potent and selective agonist for both the 5-HT2B and 5-HT2C serotonin receptor subtypes, with good selectivity over the closely related 5-HT2A subtype, and little or no affinity at other...
functionally selective over 5-HT2A, potent agonist at both 5-HT2B and 5-HT2C - VER-3323VER-3323VER-3323 is a drug which acts as a selective agonist for both the 5-HT2B and 5-HT2C serotonin receptor subtypes, with moderate selectivity for 5-HT2C, but relatively low affinity for 5-HT2A. It has potent anorectic effects in animal studies....
: selective for 5-HT2B/2C over 5-HT2A - α-Methyl-5-HT - moderately selective over 5-HT2A and 5-HT2C
Non-selective
- MDMA (Ecstasy)
- MDA
- MEM
- PergolidePergolidePergolide is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease....
- CabergolineCabergolineCabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
- NorfenfluramineNorfenfluramineNorfenfluramine is a psychoactive drug which functions as a serotonin releasing agent and potent 5HT2B receptor agonist. The action of norfenfluramine on 5HT2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the...
- ChlorphentermineChlorphentermineChlorphentermine is an appetite suppressant of the phenethylamine class. Developed in 1962, it is the 4-chloro derivative of the better known appetite suppressant phentermine, which is still in current use.Chlorphentermine itself is a relatively weak stimulant with little abuse potential, but is...
- AminorexAminorexAminorex is an anorectic stimulant drug of the 2-amino-5-aryl oxazoline class developed by a team at McNeil in 1962. It is closely related to 4-methylaminorex. Aminorex has been shown to have locomotor stimulant effects, lying midway between dextroamphetamine and methamphetamine...
- mCPP1-(3-Chlorophenyl)piperazinemeta-Chlorophenylpiperazine is a psychoactive drug of the phenylpiperazine class. It was initially developed in the late-1970s and used in scientific research before being sold as a designer drug in the mid-2000s...
- Bromo-dragonflyBromo-DragonFLYBromo-DragonFLY is a psychedelic hallucinogenic drug related to the phenethylamine family. Bromo-DragonFLY is considered an extremely potent hallucinogen, only slightly less potent than LSD with a normal dose in the region of 200 μg to 800 μg, and it has an extremely long duration of action up to...
- PsilocinPsilocinPsilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...
- DMTDMTDMT may refer to:In chemical substances:* Dimethyltryptamine, a psychedelic tryptamine* Dimethyl terephthalate, a polyester precursor* Desoxymethyltestosterone, a designer anabolic steroid...
- 5-MeO-DMT5-MeO-DMT5-MeO-DMT is a powerful psychedelic tryptamine. It is found in a wide variety of plant and psychoactive toad species and, like its close relatives DMT and bufotenin , it has been used as an entheogen by South American shamans for thousands of years.-Chemistry:5-MeO-DMT was first synthesized in...
Antagonists
- SarpogrelateSarpogrelateSarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. It blocks serotonin-induced platelet aggregation, and has applications in the treatment of many diseases including diabetes mellitus, Buerger's disease, Raynaud's disease, coronary artery disease, angina...
(mixed 5-HT2A / 5-HT2B antagonist) - LisurideLisurideLisuride is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base and as hydrogen maleate salt.Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks...
(primarily dopamine agonist, but 5-HT2B antagonist effects as well) - TegaserodTegaserodTegaserod is a 5-HT4 agonist manufactured by Novartis and sold under the name Zelnorm for the management of irritable bowel syndrome and constipation. Approved by the FDA in 2002, it was subsequently removed from the market in 2007 due to FDA concerns about possible adverse cardiovascular effects...
(primarily 5-HT4 agonist, but also 5-HT2B antagonist) - RS-127,445RS-127,445RS-127,445 is a drug which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with around 1000x selectivity over the closely related 5-HT2A and 5-HT2C receptors. The role of the 5-HT2B receptor in the body is still poorly understood, and RS-127,445 has been a useful tool in...
: high affinity; subtype selective (1000x), selective over at least eight other 5-HTR types; orally bioavailable. - SDZ SER-082SDZ SER-082SDZ SER-082 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors, with good selectivity over other serotonin receptor subtypes and slight preference for 5-HT2C over 5-HT2B. It has been used in animal studies into the behavioural effects of the different 5-HT2...
: mixed 5-HT2B/2C antagonist - EGIS-7625: high selectivity over 5-HT2A
- PRX-08066PRX-08066PRX-08066 is a drug developed by EPIX Pharmaceuticals, which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with a 5-HT2B binding affinity of 3.4nM, and high selectivity over the closely related 5-HT2A and 5-HT2C receptors and other receptor targets...
- SB-200,646
- SB-204,741SB-204,741SB-204,741 is a drug which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with around 135x selectivity over the closely related 5-HT2C receptor, and even higher over the 5-HT2A receptor and other targets. It is used in scientific research for investigating the functions...
- SB-206,553SB-206,553SB-206,553 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors. It has anxiolytic properties in animal studies and interacts with a range of other drugs. It has also been shown to act as a positive allosteric modulator of α7 nicotinic acetylcholine receptors....
: mixed 5-HT2B / 5-HT2C antagonist and PAM at α7 nAChR - SB-215,505SB-215,505SB-215,505 is a drug which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with good selectivity over the related 5-HT2A and 5-HT2C receptors...
- SB-228,357
- LY-272,015LY-272,015LY-272,015 is a beta-carboline derivative drug developed by Eli Lilly, which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor. It has anti-hypertensive effects in animal models, and is also used in research into the other functions of the 5-HT2B receptor....
Possible Applications
5-HT2B antagonists have previously been proposed as treatment for migraineMigraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
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 heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
.