Pharmacology and stereoselectivity of structurally novel cannabinoids in mice.
Pharmacology and stereoselectivity of structurally novel cannabinoids in mice.
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发表时间：
1988-12
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通讯作者：
P. J. Little;D. R. Compton;M. Johnson;L. Melvin;B. Martin
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作者：
P. J. Little;D. R. Compton;M. Johnson;L. Melvin;B. Martin
三个立体异构体对结构新颖的大麻素的药理作用进行了测试后，静脉注射给药的自发活动和生产的低温，抗伤害和僵住症的抑郁症的小鼠。（-）-对映异构体的效力比Δ 9-6a，10a-反式-四氢大麻酚高770倍，并且比它们各自的（+）-对映异构体高7至2000倍。大麻素诱导效应的效力顺序为自发活动大于抗伤害感受大于体温过低大于或等于僵住症。左南曲多在0.123至1.5 mg/kg之间具有活性，而其（+）-对映体右南曲多无活性。缺少二氢吡喃环的（-）-CP 55，244和（-）-CP 55，940类似物比δ 9- 6 α，10 α-反式-四氢大麻酚的效力高5至775倍，比它们各自的（+）-对映体的效力高30至2000倍。（+）-CP 55，243和（-）-CP 56，667的作用有一定的分离，它们在产生体温过低和僵住症方面没有活性，但在自发活动和甩尾过程中有活性。这些非经典大麻素的高度对映体选择性和效力表明了高度特异性的作用机制，如受体。
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.