Pechnick R N, Wong C A, George R, Thurkauf A, Jacobson A E, Rice K C
Department of Pharmacology, U.C.L.A. School of Medicine 90024-1735.
Neuropharmacology. 1989 Aug;28(8):829-35. doi: 10.1016/0028-3908(89)90175-5.
Some of the dioxolanes produce pharmacological effects that have much in common with phencyclidine and phencyclidine-like drugs. Dioxadrol can be resolved into two enantiomers, dexoxadrol and levoxadrol. Dexoxadrol has an affinity for phencyclidine receptors that is much greater than that of levoxadrol, but dexoxadrol and levoxadrol have nearly equal affinities for sigma receptors. The systematic analysis of the relative potencies of dexoxadrol and levoxadrol can be used as an approach to define effects mediated by phencyclidine vs sigma receptors. Compounds that act on phencyclidine receptors, as well as affecting behavior, alter body temperature in the rat. The purpose of the present study was to compare and contrast the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat. Dexoxadrol and levoxadrol (5.0, 10.0, 20.0 or 40.0 mg/kg), MK-801 (0.12, 0.6 or 1.2 mg/kg) or phencyclidine (5.0, 10.0 or 20.0 mg/kg) were administered subcutaneously and body temperature was measured. Both dexoxadrol and MK-801 produced hyperthermia but levoxadrol did not affect body temperature. In contrast to the hyperthermic effects of dexoxadrol and MK-801, phencyclidine produced hypothermia. These findings indicate that hypothermia induced by phencyclidine is not due to interactions with phencyclidine receptors and, while dexoxadrol, MK-801 and phencyclidine may share some similar receptor binding and behavioral characteristics, they can be differentiated on the basis of their effects on body temperature.
一些二氧戊环类化合物产生的药理作用与苯环利定及苯环利定样药物有很多共同之处。二氧卓醇可拆分为两种对映体,右二氧卓醇和左二氧卓醇。右二氧卓醇对苯环利定受体的亲和力远大于左二氧卓醇,但右二氧卓醇和左二氧卓醇对σ受体的亲和力几乎相等。对右二氧卓醇和左二氧卓醇相对效价的系统分析可作为一种方法来界定由苯环利定受体与σ受体介导的效应。作用于苯环利定受体的化合物,除了影响行为外,还会改变大鼠的体温。本研究的目的是比较和对比急性给予右二氧卓醇、左二氧卓醇、MK - 801和苯环利定对大鼠体温的影响。皮下注射右二氧卓醇和左二氧卓醇(5.0、10.0、20.0或40.0 mg/kg)、MK - 801(0.12、0.6或1.2 mg/kg)或苯环利定(5.0、10.0或20.0 mg/kg),并测量体温。右二氧卓醇和MK - 801均引起体温升高,但左二氧卓醇不影响体温。与右二氧卓醇和MK - 801的升温作用相反,苯环利定引起体温降低。这些发现表明,苯环利定诱导的体温降低并非由于与苯环利定受体的相互作用,而且虽然右二氧卓醇、MK - 801和苯环利定可能具有一些相似的受体结合和行为特征,但它们可根据对体温的影响加以区分。