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 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. 5-HT is short for 5-hydroxy-tryptamine, which is serotonin. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones.
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.
5-Fluoro-α-methyltryptamine, also known as PAL-544, is a putative stimulant, entactogen, and psychedelic tryptamine derivative related to α-methyltryptamine (αMT). It has been found to act as a well-balanced serotonin-norepinephrine-dopamine releasing agent, a 5-HT2A receptor agonist, and a potent and specific MAO-A inhibitor. It produces a strong head-twitch response in mice, and this effect is known to correlate with psychedelic effects in humans, which suggests that 5-fluoro-αMT could be an active psychedelic in humans, although it is not known to have been tested in humans and could be dangerous due to its strong inhibition of MAO-A.
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.
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).
8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, PD-116,948) is a drug which acts as a potent and selective antagonist for the adenosine A1 receptor. It has high selectivity for A1 over other adenosine receptor subtypes, but as with other xanthine derivatives DPCPX also acts as a phosphodiesterase inhibitor, and is almost as potent as rolipram at inhibiting PDE4. It has been used to study the function of the adenosine A1 receptor in animals, which has been found to be involved in several important functions such as regulation of breathing and activity in various regions of the brain, and DPCPX has also been shown to produce behavioural effects such as increasing the hallucinogen-appropriate responding produced by the 5-HT2A agonist DOI, and the dopamine release induced by MDMA, as well as having interactions with a range of anticonvulsant drugs.
WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent antagonist at the former receptor. It is closely related to WAY-100135.
Quipazine is a serotonergic drug of the piperazine group which is used in scientific research. It was originally intended as an antidepressant but never developed for medical use.
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.
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.
7-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with reasonable selectivity for the D3 receptor subtype, and low affinity for serotonin receptors, unlike its structural isomer 8-OH-DPAT. 7-OH-DPAT is self-administered in several animal models, and is used to study addiction to cocaine.
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-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with selectivity for the D2 receptor and D3 receptor subtypes. Only the (S)-enantiomer is active as an agonist, with the (R)-enantiomer being a weak antagonist at D2 receptors. Radiolabelled 11C-5-OH-DPAT is used as an agonist radioligand for mapping the distribution and function of D2 and D3 receptors in the brain, and the drug is also being studied in the treatment of Parkinson's disease.
GR-113808 is a drug which acts as a potent and selective 5-HT4 serotonin receptor antagonist. It is used in researching the roles of 5-HT4 receptors in various processes, and has been used to test some of the proposed therapeutic effects of selective 5-HT4 agonists, such as for instance blocking the nootropic effects of 5-HT4 agonists, and worsening the respiratory depression produced by opioid analgesic drugs, which appears to be partly 5-HT4 mediated and can be counteracted by certain 5-HT4 agonists.
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.
The head-twitch response (HTR) is a rapid side-to-side head movement that occurs in mice and rats after the serotonin 5-HT2A receptor is activated. The prefrontal cortex may be the neuroanatomical locus mediating the HTR. Many serotonergic hallucinogens, including lysergic acid diethylamide (LSD), induce the head-twitch response, and so the HTR is used as a behavioral model of hallucinogen effects. However while there is generally a good correlation between compounds that induce head twitch in mice and compounds that are hallucinogenic in humans, it is unclear whether the head twitch response is primarily caused by 5-HT2A receptors, 5-HT2C receptors or both, though recent evidence shows that the HTR is mediated by the 5-HT2A receptor and modulated by the 5-HT2C receptor. Also, the effect can be non-specific, with head twitch responses also produced by some drugs that do not act through 5-HT2 receptors, such as phencyclidine, yohimbine, atropine and cannabinoid receptor antagonists. As well, compounds such as 5-HTP, fenfluramine and 1-Methylpsilocin can also produce head twitch and do stimulate serotonin receptors, but are not hallucinogenic in humans. This means that while the head twitch response can be a useful indicator as to whether a compound is likely to display hallucinogenic activity in humans, the induction of a head twitch response does not necessarily mean that a compound will be hallucinogenic, and caution should be exercised when interpreting such results.
5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs). It has been investigated in animals as a potential treatment for cocaine dependence. The EC50 values of 5-chloro-αMT in evoking the in vitro release of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA. However, 5-chloro-αMT has also been found to act as a potent full agonist of the 5-HT2A receptor, with an EC50 value of 6.27 nM and an efficacy of 105%, and almost assuredly acts as a potent agonist of other serotonin receptors as well.
