5-HT₆ Receptor Agonist

Norpsilocin (4-hydroxy-N-methyltrypt amine; 4-HO-NMT) is a natural tryptamine alkaloid isolated from the hallucinogenic mushroom Psilocybe cubensis. Norpsilocin activates human 5-HT2 receptors (5-HT2A: EC₅₀ = 8.4 nM; 5-HT2B = 12.8 nM; 5-HT2C = 39.6 nM) and displays binding affinity toward 5-HT1 receptors (5-HT1B: K_i = 212 nM; 5-HT1D = 48.9 nM; 5-HT1E = 81.7 nM). Norpsilocin induces β-arrestin recruitment at the 5-HT1B receptor. Norpsilocin fails to produce psychedelic-like effects in mice, whereas high doses can induce hypothermia in vivo. Norpsilocin acts as an important research tool for exploring the structure–activity relationship of tryptamine hallucinogens and the pharmacology of serotonin receptors.

WAY-181187 (SAX-187) is a potent and selective full 5-HT6 receptor agonist with a K_i of 2.2 nM and an EC₅₀ of 6.6 nM. WAY181187 mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist.

WAY 208466 dihydrochloride is a potent and selective 5-HT₆ receptor agonist (EC₅₀=7.3 nM for the human 5-HT₆ receptor). WAY-208466 dihydrochloride elevates cortical GABA levels in rat frontal cortex. WAY 208466 dihydrochloride exhibits antidepressant and anxiolytic-like effects.

EMD386088 is a potent and selective 5-HT6 receptor (5-HT6R) agonist with an EC₅₀ of 1.0 nM. EMD-386088 is inactive against other HT receptors except 5-HT3R (IC₅₀ of 34 nM). EMD386088 regulates the activity of ERK1/2. EMD386088 has the potential for the research of alzheimer's disease (AD) and schizophrenia.

ST1936 is a selective, nanomolar affinity 5-HT₆ receptor agonist with K_i values of 13 nM, 168 nM and 245 nM for human 5-HT₆, 5-HT₇ and 5-HT_2B receptors, respectively. ST1936 also shows moderate affinity (K_i of 300 nM) for human and rat α2 adrenergic receptor.

E6801 is a 5-HT6 receptor agonist that improves recognition memory by jointly modulating cholinergic and glutamatergic neurotransmission. E6801 can be used in studies of dementia, depression, obesity, epilepsy, etc.

5-HT_1AR agonist 2 (Compound 4f) is a 5-HT_1A receptor agonist (K_i: 10.0 nM). 5-HT_1AR agonist 2 also binds to the SERT, D₂ receptor and 5-HT₆ receptor (K_i: SERT, 2.8 nM; D₂, 23 nM; 5-HT₆, 192 nM). 5-HT_1AR agonist 2 is stabilized in microsomes and induces hypothermia in mice.

5-HT6/5-HT2AR antagonist-1 is a potent dual 5-HT₆/5-HT_2AR antagonist with K_i values of 11 nM and 39 nM, respectively.

WAY-181187 (SAX-187) oxalate is a potent and selective full 5-HT6 receptor agonist with a K_i of 2.2 nM and an EC₅₀ of 6.6 nM. WAY-181187 oxalate mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist.

WAY-181187 (SAX-187) hydrochloride is a potent and selective full 5-HT6 receptor agonist with a K_i of 2.2 nM and an EC₅₀ of 6.6 nM. WAY-181187 hydrochloride mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist.

ST1936 oxalate is a selective, nanomolar affinity 5-HT₆ receptor agonist with K_i values of 13 nM, 168 nM and 245 nM for human 5-HT₆, 5-HT₇ and 5-HT_2B receptors, respectively. ST1936 oxalate also shows moderate affinity (K_i of 300 nM) for human and rat α2 adrenergic receptor.

EMDT oxalate is a selective 5-HT6 agonist, and has antidepressant effects.

WAY 208466 is a selective 5-HT6 receptor agonist with an EC₅₀ of 7.3 nM. WAY-208466 increases GABA levels following both acute and chronic administration in the dorsolateral frontal cortex of rat models with stereotaxic surgery. WAY 208466 can be used for anxiety-related disorders like obsessive compulsive disorder (OCD) research.