Little P J, Compton D R, Johnson M R, Melvin L S, Martin B R
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
J Pharmacol Exp Ther. 1988 Dec;247(3):1046-51.
The pharmacological effects of three stereoisomeric pairs of structurally novel cannabinoids were tested after i.v. administration in mice for depression of spontaneous activity and the production of hypothermia, antinociception and catalepsy. The (-)-enantiomers were as much as 770 times more potent than delta 9-6a,10a-trans-tetrahydrocannabinol and were 7 to 2000 times more potent than their respective (+)-enantiomers. The order of potency for cannabinoid-induced effects was spontaneous activity greater than antinociception greater than hypothermia greater than or equal to catalepsy. Levonantradol was active between 0.123 to 1.5 mg/kg, whereas dextronantradol, its (+)-enantiomer was inactive. (-)-CP 55,244 and (-)-CP55,940 analogs which lack the dihydropyran ring were 5 to 775 times more potent than delta 9-6a,10a-trans-tetrahydrocannabinol and 30 to 2000 times more potent than their respective (+)-enantiomers. Some separation of effects was demonstrated with (+)-CP 55,243 and (-)-CP 56,667 which were inactive in producing hypothermia and catalepsy but were active in the spontaneous activity and tail-flick procedures. The high degree of enantioselectivity and potency of these nonclassical cannabinoids are indicative of a highly specific mechanism of action such as a receptor.
在小鼠静脉注射后，测试了三对结构新颖的大麻素立体异构体对自发活动的抑制、体温降低、抗伤害感受和僵住症的药理作用。（-）-对映体的效力比δ9-6a,10a-反式-四氢大麻酚高770倍，比其各自的（+）-对映体高7至2000倍。大麻素诱导效应的效力顺序为自发活动＞抗伤害感受＞体温降低≥僵住症。左南曲朵在0.123至1.5毫克/千克之间有活性，而其（+）-对映体右南曲朵无活性。缺乏二氢吡喃环的（-）-CP 55,244和（-）-CP55,940类似物比δ9-6a,10a-反式-四氢大麻酚效力高5至775倍，比其各自的（+）-对映体高30至2000倍。（+）-CP 55,243和（-）-CP 56,667在产生体温降低和僵住症方面无活性，但在自发活动和甩尾试验中有活性，显示出一些效应分离。这些非经典大麻素的高度对映选择性和效力表明其作用机制具有高度特异性，如受体。
