Tateyama M, Ohta S, Nagao T, Hirobe M, Ono H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Neuropharmacology. 1993 Mar;32(3):243-8. doi: 10.1016/0028-3908(93)90107-e.
4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 micrograms), injected unilaterally into the nucleus accumbens, increased ambulation. Alone, 4-PTIQ (10 micrograms) failed to elicit ambulation; however, it inhibited the methamphetamine-induced increase in ambulation. The alpha 1-antagonist prazosin (0.5 micrograms) or the beta-antagonist propranolol (3 micrograms) showed no effect on ambulation induced by methamphetamine. Haloperidol (5 ng), which possesses strong dopamine-blocking activity, abolished the ambulation induced by methamphetamine. The drug 4-PTIQ had weak affinity for dopamine D1 and D2 receptors. These results support the possibility that the inhibitory effects of 4-PTIQ on the ambulation-stimulating effects of methamphetamine, are due to blocking of the dopamine-releasing effect of methamphetamine but not due to dopamine blocking effects.
4-苯基-1,2,3,4-四氢异喹啉（4-PTIQ）先前已被证明在脊髓中对甲基苯丙胺具有拮抗特性。给大鼠皮下注射4-PTIQ（5毫克/千克）可减少由皮下注射甲基苯丙胺（0.5毫克/千克）诱导的活动。单侧注射到伏隔核中的甲基苯丙胺（3微克）会增加活动。单独使用时，4-PTIQ（10微克）不会引起活动；然而，它会抑制甲基苯丙胺诱导的活动增加。α1拮抗剂哌唑嗪（0.5微克）或β拮抗剂普萘洛尔（3微克）对甲基苯丙胺诱导的活动没有影响。具有强多巴胺阻断活性的氟哌啶醇（5纳克）可消除甲基苯丙胺诱导的活动。药物4-PTIQ对多巴胺D1和D2受体具有弱亲和力。这些结果支持了4-PTIQ对甲基苯丙胺活动刺激作用的抑制作用可能是由于阻断了甲基苯丙胺的多巴胺释放作用而非多巴胺阻断作用的可能性。
