Deschloroketamine (10 mg/kg) and diphenidine (10-60 mg/kg) produced increased locomotor activation and stereotypy similar to ketamine (10 mg/kg) in mice. Both substances increased preference for the drug-paired compartment in conditioned place preference testing, indicating rewarding effects. In self-administration tests, deschloroketamine (1 mg/kg/infusion) increased active lever presses and infusions, suggesting reinforcing effects, whereas diphenidine (1, 2 mg/kg/infusion) did not alter these measures. Both compounds increased dopamine levels in PC-12 cells. The data suggest deschloroketamine may have both rewarding and reinforcing effects, while diphenidine only induced rewarding effects.
Methamnetamine (PAL-1046), an amphetamine-based new psychoactive substance that causes excessive serotonin release, is not regulated in most countries and had no prior metabolism studies. Using human liver microsomes and flavin-containing monooxygenase analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry, eight phase I metabolites were identified. Metabolic processes include N-demethylation, N-hydroxylation, and aromatic hydroxylation. N-hydroxylated metabolites were confirmed using expressed FMOs. The major metabolite results from hydroxylation of the naphthalene ring. These findings may help detect methamnetamine ingestion by users.