title: Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232.
abstract: The aminotetralins (+)-AJ76 and (+)-UH232 are stimulant dopaminergic antagonists, which may preferentially antagonize autoreceptors of dopamine nerve terminals. Both agents antagonized cocaine's depressant effects on firing rates of ventral tegmental dopaminergic neurons, but (+)-UH232 was much more potent. When injected simultaneously with cocaine, (+)-UH232 inhibited and (+)-AJ76 enhanced the locomotor stimulation observed during the first 30 min following s.c. cocaine administration. However, (+)-AJ76 antagonized cocaine-induced stereotypies as well as the later more intense cocaine locomotor stimulation. It is suggested that preferential dopamine autoreceptor antagonists may provide a novel approach to a pharmacotherapy for treating cocaine abuse.
authors.affiliation: Upjohn Co., Kalamazoo, MI 49001.
authors.forename: M F
authors.initials: MF
authors.lastname: Piercey
authors.forename: J T
authors.initials: JT
authors.lastname: Lum
authors.forename: W E
authors.initials: WE
authors.lastname: Hoffmann
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: E
authors.initials: E
authors.lastname: Ljung
authors.forename: K
authors.initials: K
authors.lastname: Svensson
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D004594:Electrophysiology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; C045971:UH 232; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid