Asimilobine, also known as (R)-1-methoxy-2-hydroxynoraporphine, is a noraporphine alkaloid with various known pharmacological actions. It has been found to act as a selective biased partial agonist of the serotonin 5-HT2C receptor, with an EC50Tooltip half-maximal effective concentration of 308nM and EmaxTooltip maximal efficacy of 86% for activation of Gq signaling and no β-arrestin2 recruitment. Conversely, asimilobine was inactive as an agonist of the serotonin 5-HT2A and 5-HT2B receptors, but did show weak antagonism of these receptors at very high concentrations (IC50Tooltip half-maximal inhibitory concentration = >10,000nM). Derivatives and analogues of asimilobine with more potent serotonin 5-HT2C receptor agonism, such as 11-chloroasimilobine, have been studied and described. In addition, derivatives with dual highly potent serotonin 5-HT2A and 5-HT2C receptor agonism, such as 11-methoxyasimilobine, have been described.

(RS)-Asimilobine.

Although asimilobine is inactive as an agonist of the serotonin 5-HT2A and 5-HT2C receptors, the racemic form of the compound has been found to act as an agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, with EC50 (Emax) values of 318nM (55%), 794nM (25%), and 51nM (94%), respectively. The 1-propoxy homologue shows more potent serotonin 5-HT2A and 5-HT2B receptor agonism and less potent serotonin 5-HT2C receptor agonism (EC50 (Emax) = 43nM (91%), 53nM (81%), and 197nM (98%), respectively).

See also