title: [INCREMENT]9-Tetrahydrocannabinol discriminative stimulus effects of AM2201 and related aminoalkylindole analogs in rats.
abstract: The recent recreational use of synthetic cannabinoid ligands, collectively referred to as 'Spice', has raised concerns about their safety and possible differences in their biological effect(s) from marijuana/Δ-tetrahydrocannabinol (THC). AM2201, a highly efficacious, potent cannabinoid receptor 1 (CB1R) agonist, is a recently detected compound in 'Spice' preparations. Furthermore, structural analogs of AM2201 are now being found in 'Spice'. The present studies were conducted to investigate their Δ-THC-like effects using drug (Δ-THC) discrimination in rats. Results show that the tested compounds were potent cannabinergics that generalized to the response to Δ-THC, with AM2201 being most potent, exhibiting a 14-fold potency difference over Δ-THC. The other analogs were between 2.5-fold and 4-fold more potent than THC. Surmountable antagonism of AM2201 with the selective CB1R antagonist/inverse agonist rimonabant also established that the discrimination is CB1R dependent. Time-course data reveal that AM2201 likely peaks rapidly with an in-vivo functional half-life of only 60 min. The present data confirm and extend previous observations regarding Δ-THC-like effects of 'Spice' components.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Torbjörn U C
authors.initials: TU
authors.lastname: Järbe
authors.forename: Roger S
authors.initials: RS
authors.lastname: Gifford
authors.forename: Alexander
authors.initials: A
authors.lastname: Zvonok
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C582337:1-(5-fluoropentyl)-3-(1-naphthoyl)indole; D007211:Indoles; D011619:Psychotropic Drugs; D013759:Dronabinol