Pharmacological characterizationof synthetic cannabinoid MAM-2201:radioligand binding and abuse-related effects / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Over 30% of all new psychoactive substances identified by the UN Office on Drugs and Crime in 2016 were synthetic cannabinoids. The recent emergence of MAM-2201 on the illicit market is troubling because this drug has no precedent in either the scientific or patent literature, and appears to be a novel compound developed specifically as a ″graymarket″ drug of abuse bystruc?turally combining the known synthetic cannabinoids JWH- 122 and AM- 2201. There is currently no published information regarding the pharmacology of MAM-2201. METHODS The present studies characterized cannabinoid-like effects of MAM-2201 in vitro (interactions with cannabinoid type 1 receptors [CB1Rs]) and in vivo (in mice and rats). RESULTS In a radioligand binding assay using [3H]CP55,940 in HEK cell membranes transfected with the CB1R, MAM-2201 (Ki=5.4 nmol·L- 1), had higher binding affinity than WIN 55,212-2 (Ki=80 nmol·L-1), and D9-THC (Ki=8.3 nmol·L-1). The Emax values for MAM-2201 and WIN 55,212-2 in an assay of agonist inhibition of forskolin-stimulated cAMP were 85% (EC50=0.45 nmol·L-1) and 95%, respectively, as compared with the D9-THC Emax of 74%. In mice, MAM-2201 (0.003-1.0 mg·kg-1, IP) produced dose-dependent cannabimimetic effects which were both more potent and more effective than those of D9-THC. MAM-2201 and D9-THC dose-dependently produced hypothermiaED50=0.287 and 25.4 mg·kg-1, analgesia ED50=0.125 and 29.4 mg·kg-1, and catalepsy ED50=0.301 and 18.9 mg·kg-1 in adult male CD1 mice. Importantly, MAM-2201 also elicited convulsant effects at a dose of 1.0 mg·kg-1 in 8/8 murine subjects. In rats, MAM-2201 produced dose-dependent D9-THC-like intero?ceptive effects in subjects trained to discriminate 3.0 mg·kg-1 (IP) D9-THC from saline. CONCLUSION MAM-2201 binds CB1Rs with high affinity and agonist efficacy, and functions as a potent cannabinoid agonist in vivo across several complementary measures of cannabinoid activity in two rodent species.