Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232.
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.
Piercey
M F
MF
Upjohn Co., Kalamazoo, MI 49001.
Lum
J T
JT
Hoffmann
W E
WE
Carlsson
A
A
Ljung
E
E
Svensson
K
K
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*
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