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.
The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.
5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.
8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor full agonists to have been discovered.
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.
5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene. Agonists and antagonists for 5-HT receptors, as well as serotonin uptake inhibitors, present promnesic (memory-promoting) and/or anti-amnesic effects under different conditions, and 5-HT receptors are also associated with neural changes.
The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.
The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.
SB-204741 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 of the 5-HT2B receptor.
CP-94253 is a drug which acts as a potent and selective serotonin 5-HT1B receptor agonist, with approximately 25× and 40× selectivity over the closely related 5-HT1D and 5-HT1A receptors. It has a range of behavioral effects, based on animal testing. The effects include the following: promoting wakefulness by increasing dopamine release in the brain; reducing food intake and promoting satiety; enhancing the reinforcing effects of cocaine; and possible antidepressant effects. A recent study found that "Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA [self-administration] and decreased cue reactivity" suggesting that agonism of the inhibitory 5-HT2B receptors may diminish the cognitive reward of cocaine usage and increased use of the drug without a period of abstinence may be a product of test subjects trying to achieve a previously rewarding experience through larger dosages of cocaine.
BRL-15,572 is a drug which acts as a selective antagonist for the serotonin receptor subtype 5-HT1D, with around 60x selectivity over other related receptors. The 5-HT1D receptor has a very similar pharmacology to the closely related 5-HT1B receptor, and most older ligands for these receptors bind to both subtypes with approximately equal affinity, so development of compounds such as BRL-15572 which are able to selectively block the 5-HT1D subtype while leaving 5-HT1B unaffected, have been a significant advance which has helped scientists in researching the function of these serotonin receptor subtypes. One function of the 5-HT1D receptor this research has revealed is its role in modulating release of the neurotransmitter glutamate in the brain, as well as functions in regulation of cerebral blood pressure which are important in the pathogenesis of migraine headaches.
SB-216641 is a drug which is a selective antagonist for the serotonin receptor 5-HT1B, with around 25x selectivity over the closely related 5-HT1D receptor. It is used in scientific research, and has demonstrated anxiolytic effects in animal studies.
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.
GR-127935 is a drug which acts as a selective antagonist at the serotonin receptors 5-HT1B and 5-HT1D. It has little effect when given by itself but blocks the antiaggressive effect of 5-HT1B agonists, and alters release of serotonin in the brain, as well as reducing drug-seeking behaviour in cocaine addicted rats.
Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.
Pruvanserin is a selective 5-HT2A receptor antagonist which was under development by Eli Lilly and Company for the treatment of insomnia. It was in phase II clinical trials in 2008 but appears to have been discontinued as it is no longer in the company's development pipeline. In addition to its sleep-improving properties, pruvanserin has also been shown to have antidepressant, anxiolytic, and working memory-enhancing effects in animal studies.
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.
SB-206553 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. Modified derivatives of SB-206553 have been used to probe the structure of the 5-HT2B receptor.
SB-243213 is a research chemical which acts as a selective inverse agonist for the 5HT2C receptor and has anxiolytic effects. It has better than 100x selectivity for 5-HT2C over all other receptor subtypes tested, and a longer duration of action compared to older 5-HT2C antagonist ligands.
LY-393558 is a potent serotonin reuptake inhibitor and antagonist of the 5-HT1B, 5-HT1D, and 5-HT2A receptors. LY-393558 was also found to reduce serotonin-induced vasoconstriction, indicating that it may have therapeutic potential for the treatment of pulmonary hypertension.
