5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. [5] [6] 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.
First discovered in the stomach of rats, 5-HT2B was challenging to characterize initially because of its structural similarity to the other 5-HT2 receptors, particularly 5-HT2C. [7] The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT2B receptor is expressed in several areas of the CNS, including the dorsal hypothalamus, frontal cortex, medial amygdala, and meninges. [8] However, its most important role is in the peripheral nervous system (PNS) where it maintains the viability and efficiency of the cardiac valve leaflets. [9]
The 5-HT2B receptor subtype is involved in:
5-HT2B receptors have been strongly implicated in causing drug-induced valvular heart disease. [21] [22] [23] The Fen-Phen scandal in the 80s and 90s revealed the cardiotoxic effects of 5-HT2B stimulation. [24] Today, 5-HT2B agonism is considered a toxicity signal precluding further clinical development of a compound. [25]
The structure of the 5-HT2B receptor was resolved in a complex with the valvulopathogenic drug ergotamine. [26] 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. [27]
5-HT2B antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued. [47] More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease. [48] [49] Research claims serotonin 5-HT2B receptors have effect on liver regeneration. [50] Antagonism of 5-HT2B may attenuate fibrogenesis and improve liver function in disease models in which fibrosis is pre-established and progressive.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Aliases | HTR2B, 5-HT(2B), 5-HT2B, 5-HT-2B, 5-hydroxytryptamine receptor 2B | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 601122 MGI: 109323 HomoloGene: 55492 GeneCards: HTR2B | ||||||||||||||||||||||||||||||||||||||||||||||||||
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5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. [5] [6] 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.
First discovered in the stomach of rats, 5-HT2B was challenging to characterize initially because of its structural similarity to the other 5-HT2 receptors, particularly 5-HT2C. [7] The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT2B receptor is expressed in several areas of the CNS, including the dorsal hypothalamus, frontal cortex, medial amygdala, and meninges. [8] However, its most important role is in the peripheral nervous system (PNS) where it maintains the viability and efficiency of the cardiac valve leaflets. [9]
The 5-HT2B receptor subtype is involved in:
5-HT2B receptors have been strongly implicated in causing drug-induced valvular heart disease. [21] [22] [23] The Fen-Phen scandal in the 80s and 90s revealed the cardiotoxic effects of 5-HT2B stimulation. [24] Today, 5-HT2B agonism is considered a toxicity signal precluding further clinical development of a compound. [25]
The structure of the 5-HT2B receptor was resolved in a complex with the valvulopathogenic drug ergotamine. [26] 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. [27]
5-HT2B antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued. [47] More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease. [48] [49] Research claims serotonin 5-HT2B receptors have effect on liver regeneration. [50] Antagonism of 5-HT2B may attenuate fibrogenesis and improve liver function in disease models in which fibrosis is pre-established and progressive.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.