Methamphetamine antagonistic property of (+)- and (-)-4-phenyltetrahydroisoquinoline in rat anococcygeus muscle.
The antagonistic effects of (+)- and (-)-4-phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ) on methamphetamine in the rat anococcygeus muscle were compared with those of cocaine and nomifensine. Methamphetamine contracted the anococcygeus muscle through the release of norepinephrine from noradrenergic nerve terminals. (+)-4PTIQ inhibited the methamphetamine-induced contractions more strongly than cocaine and nomifensine. (+)-4PTIQ had no potentiating effects on exogenous norepinephrine-induced contraction, which was considered to be an index of amine neuronal uptake blockade. On the other hand, (-)-4PTIQ, cocaine and nomifensine produced a significant leftward shift of the norepinephrine concentration-response curve, i.e. they showed a strong blocking effect on amine neuronal uptake. These results suggest that the inhibitory effects of (+)-4PTIQ on the action of methamphetamine are mediated by a mechanism other than inhibition of amine neuronal uptake.
Watanabe
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Tateyama
M
M
Nagao
T
T
Ohta
S
S
Hirobe
M
M
Ono
H
H
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008729:Methoxamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D009627:Nomifensine; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline; D016627:Oxidopamine; D008729:Methoxamine; D003042:Cocaine; D009638:Norepinephrine