Iwamoto E T
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536.
Life Sci. 1989;44(21):1547-54. doi: 10.1016/0024-3205(89)90448-7.
Evidence for a drug-induced activation of central sigma systems is presented. The model is the locomotor activation initiated by a subcutaneous (SC) challenge of 1.6 mg/kg of (+)-butaclamol, (+)-BUT, given 30 min before 10 mg/kg SC of (-)-N-allylnormetazocine, (-)-NAN, in Sprague-Dawley male rats which have been pretreated with four daily injections of 10 mg/kg SC of (-)-NAN. The locomotor activation is characterized by an initial 20 min period of retropulsion and sideways-circling followed by 90 to 100 min of forward locomotion. The locomotor syndrome is antagonized by 10 mg/kg of (+/-)-BMY 14802, 20 mg/kg of rimcazole, and 0.2 mg/kg of haloperidol, but not by 0.04 mg/kg of R(+)SCH23390, 100 mg/kg of S(-)sulpiride, 10 mg/kg of naltrexone, or 2.5 mg/kg of MR2266. The data suggest that the manifestation of the (+)-BUT/(-)-NAN-induced syndrome depends upon intact transmission at central sigma sites.
本文提供了药物诱导中枢西格玛系统激活的证据。实验模型是在经每日4次皮下注射10mg/kg（-）-烯丙基去甲左啡诺（-）-NAN预处理的Sprague-Dawley雄性大鼠中，在皮下注射10mg/kg（-）-烯丙基去甲左啡诺（-）-NAN前30分钟，皮下注射1.6mg/kg（+）-布他拉莫（+）-BUT引发的运动激活。运动激活的特征是最初20分钟的后推和侧向转圈，随后是90至100分钟的向前运动。运动综合征可被10mg/kg（±）-BMY 14802、20mg/kg利咪唑和0.2mg/kg氟哌啶醇拮抗，但不能被0.04mg/kg R（+）-SCH23390、100mg/kg S（-）-舒必利、10mg/kg纳曲酮或2.5mg/kg MR2266拮抗。数据表明，（+）-BUT/（-）-NAN诱导综合征的表现取决于中枢西格玛位点的完整传递。
