Amphetamine-antagonistic properties of 4-phenyl-1,2,3,4- tetrahydroisoquinoline: inhibition of spinal reflex-enhancing effects of methamphetamine, phenylethylamine and nomifensine.
The antagonistic effects of 4-phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ) against S(+)-methamphetamine, phenylethylamine and nomifensine were studied by measurement of spinal monosynaptic reflex potential (MSR). S(+)-Methamphetamine, phenylethylamine and nomifensine enhanced the amplitude of MSR in C1-spinalized rats through release of noradrenaline from the terminals of descending fibers and consequent activation of alpha 1-adrenoceptors. Although 4PTIQ alone did not change the amplitude of the MSR, 4PTIQ inhibited the enhancement of MSR induced by S(+)-methamphetamine and related compounds. The MSR of rats with an intact spinal cord was enhanced by conditioning stimulation of the ipsilateral locus ceruleus. The MSR enhancement produced by the stimulation was blocked by prazosin but unaffected by 4PTIQ, showing that 4PTIQ does not have an alpha 1-blocking action. These results suggest that the antagonistic effects of 4PTIQ on MSR enhancement by S(+)-methamphetamine, phenylethylamine and nomifensine are due to its blocking of noradrenaline release produced by these amphetamine-like agents.
Ono
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Hasebe
Y
Y
Satoh
M
M
Nagao
T
T
Ohta
S
S
Hirobe
M
M
Fuduka
H
H
D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004558:Electric Stimulation; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009627:Nomifensine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D010627:Phenethylamines; D011619:Psychotropic Drugs; D044005:Tetrahydroisoquinolines; D009627:Nomifensine; C029261:phenethylamine; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline; D000661:Amphetamine; D011224:Prazosin