A simple behavioral test in mice may help regulators quickly identify new hallucinogenic drugs. Mice given the hallucinogen-like compound DOI showed aversive effects in a conditioned place aversion test and abnormal behavior in a marble-burying test. These responses likely stem from the drug's hallucinogenic properties. The findings suggest that such rodent tests could serve as a rapid, accurate screening method for designating new psychoactive substances as controlled drugs, aiding prevention of drug abuse.
Law-evading herbal products in Japan, marketed as incense or herbs, contain synthetic cannabinoids that cause disturbed consciousness, dyspnea, traffic accidents, and ambulance transports. Because many cannabinoid compounds exist, regulating one prompts substitution with a slightly different one, creating a regulatory cat-and-mouse game. The paper summarizes the pharmacological actions and dangers of synthetic cannabinoids and outlines comprehensive designations that regulate based on chemical structure similarity. The authors established a screening system using animal behavioral analysis and cell culture cytotoxicity assays to rapidly evaluate psychic-dependence liability and cytotoxicity. These data contributed to legislation for comprehensive designations of synthetic cannabinoids.
The oxidative metabolism of the tryptamine 5-MeO-DIPT (Foxy) was studied in vitro using human liver microsomes and recombinant CYP enzymes. 5-MeO-DIPT was mainly converted to two metabolites: O-demethylated (5-OH-DIPT) and N-deisopropylated (5-MeO-IPT). O-demethylation showed monophasic kinetics and was almost exclusively carried out by CYP2D6, as inhibition by quinidine completely blocked this pathway. N-deisopropylation showed triphasic kinetics and involved multiple enzymes: CYP1A2, CYP2C8, CYP3A4, and to a lesser extent CYP2C9 and CYP2C19. Inhibition studies with furafylline, quercetin, sulfaphenazole, and ketoconazole suppressed N-deisopropylation by about 60%, 45%, 15%, and 40%, respectively, at 50 μM substrate. CYP2D6 is the major O-demethylase; CYP1A2, CYP2C8, and CYP3A4 are the major N-deisopropylases in human liver.