4-Phenyltetrahydroisoquinoline, but not nomifensine or cocaine, inhibits methamphetamine-induced dopamine release.
The inhibitory effect of 4-phenyltetrahydroisoquinoline (4-PTIQ) on methamphetamine-induced dopamine release in the rat nucleus accumbens was investigated using a brain microdialysis method. Methamphetamine (10(-6) M) infusion through a microdialysis probe induced the release of dopamine. Although the uptake inhibitors, cocaine (3 x 10(-6) M) and nomifensine (10(-6) M), failed to block dopamine release, 4-PTIQ (10(-6 M) inhibited the dopamine-releasing effect of methamphetamine. 4-PTIQ did not affect the elevation of the extracellular dopamine level induced by high concentrations of nomifensine (10(-5) M) and cocaine (3 x 10(-5) M). 4-PTIQ was the weakest inhibitor of [3H]dopamine uptake by rat striatal synaptosomes. These results suggest that 4-PTIQ is a selective antagonist against the dopamine-releasing effect of methamphetamine in the nucleus accumbens.
Tateyama
M
M
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Nagao
T
T
Ohta
S
S
Hirobe
M
M
Ono
H
H
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors*; D009627:Nomifensine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D009627:Nomifensine; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline; D003042:Cocaine; D004298:Dopamine