5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT2 subfamily consists of three G protein-coupled receptors (GPCRs) which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C. For more information, please see the respective main articles of the individual subtypes:
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
meta-Chlorophenylpiperazine (mCPP) 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. It has been detected in pills touted as legal alternatives to illicit stimulants in New Zealand and pills sold as "ecstasy" in Europe and the United States.
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-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.
Xylamidine is a drug which acts as an antagonist of the serotonin 5-HT2A and 5-HT2C receptors, and to a lesser extent of the serotonin 5-HT1A receptor. The drug does not cross the blood–brain barrier and hence is peripherally selective, which makes it useful for blocking peripheral serotonergic responses like cardiovascular and gastrointestinal effects, without producing the central effects of 5-HT2A receptor blockade such as sedation, or interfering with the central actions of 5-HT2A receptor agonists.
RS-127445, also known as MT-500, is a drug which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with around 1,000-fold 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-127445 has been a useful tool in unravelling the function of the various systems in which this receptor is expressed. The drug was under development for potential use as a pharmaceutical drug by Roche and reached phase 1 clinical trials but was discontinued for unknown reasons.
RS-102221 is a drug developed by Hoffmann–La Roche, which was one of the first compounds discovered that acts as a potent and selective antagonist at the serotonin 5-HT2C receptor, with around 100× selectivity over the closely related 5-HT2A and 5-HT2B receptors. It has anxiolytic effects in animal studies, increases the effectiveness of SSRI antidepressants, and shows a complex interaction with cocaine, increasing some effects but decreasing others, reflecting a role for the 5-HT2C receptor in regulation of the dopamine signalling system in the brain.
AL-38022A is an indazole derivative drug which is one of a range of similar drugs developed for scientific research and with some possible clinical applications. It acts as a potent and selective agonist for the 5-HT2 family of serotonin receptors, with highest binding affinity for the 5-HT2C subtype and around four times less affinity for 5-HT2A and 5-HT2B. In drug discrimination tests on animals, it fully substituted for both DOM and 5-MeO-DMT.
α-Methylserotonin (αMS), also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT) or 5-hydroxy-α-methyltryptamine (5-HO-αMT), is a tryptamine derivative closely related to the neurotransmitter serotonin (5-HT). It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system.
SDZ 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 subtypes, and how they influence the effects of other drugs such as cocaine.
SB-215505 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. It is used in scientific research into the function of the 5-HT2 family of receptors, especially to study the role of 5-HT2B receptors in the heart, and to distinguish 5-HT2B-mediated responses from those produced by 5-HT2A or 5-HT2C.
1-(1-Naphthyl)piperazine (1-NP) is a drug which is a phenylpiperazine derivative. It acts as a non-selective, mixed serotonergic agent, exerting partial agonism at the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F receptors, while antagonizing the 5-HT2A, 5-HT2B, and 5-HT2C receptors. It has also been shown to possess high affinity for the 5-HT3, 5-HT5A, 5-HT6, and 5-HT7 receptors, and may bind to 5-HT4 and the SERT as well. In animals it produces effects including hyperphagia, hyperactivity, and anxiolysis, of which are all likely mediated predominantly or fully by blockade of the 5-HT2C receptor.
Glemanserin (INN) is a drug which acts as a potent and selective 5-HT2A receptor antagonist. The first truly selective 5-HT2A ligand to be discovered, glemanserin resulted in the development of the widely used and even more potent and selective 5-HT2A receptor antagonist volinanserin (MDL-100,907), which is a fluorinated analogue. Though it was largely superseded in scientific research by volinanserin, glemanserin was investigated clinically for the treatment of generalized anxiety disorder. However, it was ultimately found to be ineffective and was not marketed.
5-HT2C receptor agonists are a class of drugs that activate 5-HT2C receptors. They have been investigated for the treatment of a number of conditions including obesity, psychiatric disorders, sexual dysfunction and urinary incontinence.
25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.
Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).
BW-501C67 is a peripherally selective serotonin 5-HT2A and 5-HT2C receptor antagonist which is used in scientific research. It shows selectivity for the serotonin 5-HT2 receptors over the α1-adrenergic receptor.
