The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.
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. 5-HT is short for 5-hydroxy-tryptamine or 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.
5-Methoxytryptamine (5-MT), also known as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. 5-MT has been shown to occur naturally in the body in low levels. It is biosynthesized via the deacetylation of melatonin in the pineal gland.
5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.
5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.
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 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.
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.
LY-334370 is a selective 5-HT1F receptor agonist which was under development by Eli Lilly and Company for the treatment of migraine headaches. The drug showed efficacy in a phase II clinical trial but further development was halted due to toxicity detected in animals.
EMD-386088 is an indole derivative which is used in scientific research. It acts as a potent 5-HT6 receptor partial agonist, with a Ki of 1 nM, a significantly higher affinity than older 5-HT6 agonists such as EMDT, although it possesses moderate affinity for the 5-HT3 receptor as well. Subsequent research has determined that EMD-386088 is also a dopamine reuptake inhibitor and that this action is involved in the antidepressant-like effects of the drug in rodents.
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.
Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class. It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects. However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone. It was found to be both more potent and more selective in comparison and was commercialized instead.
Umespirone (KC-9172) is a drug of the azapirone class which possesses anxiolytic and antipsychotic properties. It behaves as a 5-HT1A receptor partial agonist (Ki = 15 nM), D2 receptor partial agonist (Ki = 23 nM), and α1-adrenoceptor receptor antagonist (Ki = 14 nM), and also has weak affinity for the sigma receptor (Ki = 558 nM). Unlike many other anxiolytics and antipsychotics, umespirone produces minimal sedation, cognitive/memory impairment, catalepsy, and extrapyramidal symptoms.
CSP-2503 is a potent and selective 5-HT1A receptor agonist, 5-HT2A receptor antagonist, and 5-HT3 receptor antagonist of the phenylpiperazine class. First synthesized in 2003, it was designed based on computational models and QSAR studies. In rat studies, CSP-2503 has demonstrated anxiolytic effects, and thus has been suggested as a treatment for anxiety in humans with a multimodal mechanism of action.
SB-258719 is a drug developed by GlaxoSmithKline which acts as a selective 5-HT7 receptor partial inverse agonist, and was the first such ligand identified for 5-HT7. Its use in research has mainly been in demonstrating the potential use for 5-HT7 agonists as potential novel analgesics, due to the ability of SB-258719 to block the analgesic effects of a variety of 5-HT7 agonists across several different testing models.
CJ-033466 is a drug which acts as a potent and selective 5-HT4 serotonin receptor partial agonist. In animal tests it stimulated gastrointestinal motility with 30 times the potency of cisapride, and with lower affinity for the hERG channel.
Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.
ST-1936 (2-methyl-5-chloro-N,N-dimethyltryptamine) is a tryptamine derivative which is used in scientific research. It acts as a selective 5-HT6 receptor agonist, with a Ki of 13 nM, and much weaker action at 5-HT2B and 5-HT7 subtypes. In animal studies it has been found to increase dopamine and noradrenaline mediated signalling but decreases glutamatergic transmission, and has antidepressant effects.
PD-137889 (N-methylhexahydrofluorenamine) is a chemical compound that is active as an NMDA receptor antagonist in the central nervous system at roughly 30 times the potency of the "flagship" of its class, ketamine, and substitutes for phencyclidine in animal studies. Ki [3H]TCP binding = 27 nM versus ketamine's Ki = 860 nM.
AC-90179 is a piperidine derivative which acts as an inverse agonist at the 5-HT2A serotonin receptor and an antagonist at 5-HT2C. It was developed as a potential antipsychotic but was not pursued for medical applications due to poor oral bioavailability, however it continues to be used as a tool compound in pharmacological research.
