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.
Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
BIMU-8 is a drug which acts as a 5-HT4 receptor selective agonist. BIMU-8 was one of the first compounds of this class. The main action of BIMU-8 is to increase the rate of respiration by activating an area of the brain stem known as the pre-Botzinger complex.
The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs) and therefore differs structurally and functionally from all other 5-HT receptors (5-hydroxytryptamine, or serotonin receptors) which are G protein-coupled receptors. This ion channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems.
The serotonin 1A receptor is a subtype of serotonin receptor, or 5-HT receptor, 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 hyperpolarisation and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.
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 be discovered.
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.
Flesinoxan (DU-29,373) is a potent and selective 5-HT1A receptor partial/near-full agonist of the phenylpiperazine class. Originally developed as a potential antihypertensive drug, flesinoxan was later found to possess antidepressant and anxiolytic effects in animal tests. As a result, it was investigated in several small human pilot studies for the treatment of major depressive disorder, and was found to have robust effectiveness and very good tolerability. However, due to "management decisions", the development of flesinoxan was stopped and it was not pursued any further.
Xylamidine is a drug which acts as an antagonist at the 5HT2A receptor, and to a lesser extent at the 5HT1A receptor. It does not cross the blood–brain barrier, which makes it useful for blocking peripheral serotonergic responses like cardiovascular and gastrointestinal effects, without producing the central effects of 5HT2A blockade such as sedation, or interfering with the central actions of 5HT2A agonists.
Prucalopride, brand names Resolor and Motegrity among others, is a drug acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalizing bowel movements. Prucalopride was approved for medical use in the European Union in 2009, in Canada in 2011, in Israel in 2014, and in the United States in December 2018. The drug has also been tested for the treatment of chronic intestinal pseudo-obstruction.
UH-232 ((+)-UH232) is a drug which acts as a subtype selective mixed agonist-antagonist for dopamine receptors, acting as a weak partial agonist at the D3 subtype, and an antagonist at D2Sh autoreceptors on dopaminergic nerve terminals. This causes dopamine release in the brain and has a stimulant effect, as well as blocking the behavioural effects of cocaine. It may also serve as a 5-HT2A receptor agonist, based on animal studies. It was investigated in clinical trials for the treatment of schizophrenia, but unexpectedly caused symptoms to become worse.
WAY-100135 is a serotonergic drug of the phenylpiperazine family which is used in scientific research. It acts as potent 5-HT1A receptor antagonist, and was originally believed to be highly selective, but further studies have demonstrated that it also acts as a partial agonist of the 5-HT1D receptor (pKi = 7.58; virtually the same affinity for 5-HT1A), and to a much lesser extent, of the 5-HT1B receptor (pKi = 5.82). These findings may have prompted the development of the related compound WAY-100635, another purportedly selective and even more potent 5-HT1A antagonist, which was synthesized shortly thereafter. However, WAY-100635 turned out to be non-selective as well, having been shown to act additionally as a potent D4 receptor agonist later on.
Befiradol is an experimental drug being studied for the treatment of levodopa-induced dyskinesia. It is a potent and selective 5-HT1A receptor full agonist.
Eptapirone (F-11,440) is a very potent and highly selective 5-HT1A receptor full agonist of the azapirone family. Its affinity for the 5-HT1A receptor was reported to be 4.8 nM (Ki), and its intrinsic activity approximately equal to that of serotonin.
Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor. Osemozotan has antidepressant, anxiolytic, antiobsessional, serenic, and analgesic effects in animal studies, and is used to investigate the role of 5-HT1A receptors in modulating the release of dopamine and serotonin in the brain, and their involvement in addiction to abused stimulants such as cocaine and methamphetamine.
5-Benzyloxytryptamine (5-BT), is a tryptamine derivative which acts as an agonist at the 5-HT1D, 5-HT2 and 5-HT6 serotonin receptors, and an antagonist of TRPM8.
ICI-199,441 is a drug which acts as a potent and selective κ-opioid agonist, and has analgesic effects. It is a biased agonist of the KOR, and is one of a relatively few KOR ligands that is G protein-biased rather than β-arrestin-biased.
S-14671 is a naphthylpiperazine derivative which acts as a 5-HT1A receptor agonist (pKi = 9.3) with high efficacy and exceptional in vivo potency, and also as a 5-HT2A and 5-HT2C receptor antagonist (both are pKi = 7.8). It displays only low and non-significant affinity for 5-HT1B and 5-HT3 sites.
SR144528 is a drug that acts as a potent and highly selective CB2 receptor inverse agonist, with a Ki of 0.6 nM at CB2 and 400 nM at the related CB1 receptor. It is used in scientific research for investigating the function of the CB2 receptor, as well as for studying the effects of CB1 receptors in isolation, as few CB1 agonists that do not also show significant activity as CB2 agonists are available. It has also been found to be an inhibitor of sterol O-acyltransferase, an effect that appears to be independent from its action on CB2 receptors.
MK-212 is a serotonin agonist. It promotes the secretion of serum prolactin and cortisol in humans.
