title: The cannabinoid CB(1) receptor antagonist SR141716A increases norepinephrine outflow in the rat anterior hypothalamus.
abstract: The effects of the selective cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide-hydrochloride (SR141716A) on extracellular concentrations of norepinephrine and 5-hydroxytryptamine (5-HT) were assessed by in vivo microdialysis in the anterior hypothalamus of freely moving rats. SR14716A (0.3, 1, 3 mg/kg, i.p.) dose-dependently increased norepinephrine efflux to about 300% of baseline, without affecting 5-HT levels. This increase in norepinephrine outflow could play an important role in the pharmacological and potentially therapeutic actions of SR141716A.
authors.affiliation: Eli Lilly & Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285-0510, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Tzavara
authors.forename: K W
authors.initials: KW
authors.lastname: Perry
authors.forename: D E
authors.initials: DE
authors.lastname: Rodriguez
authors.forename: F P
authors.initials: FP
authors.lastname: Bymaster
authors.forename: G G
authors.initials: GG
authors.lastname: Nomikos
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012701:Serotonin / Q000378:metabolism
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000077285:Rimonabant; D009638:Norepinephrine; D006719:Homovanillic Acid