Structural requirements for arachidonylethanolamide interaction with CB1 and CB2 cannabinoid receptors:: pharmacology of the carbonyl and ethanolamide groups

被引:21
作者
Berglund, BA
Boring, DL
Wilken, GH
Makriyannis, A
Howlett, AC
机构
[1] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA
[2] US FDA, Ctr Drug Evaluat & Res, Div New Drug Synth, Rockville, MD 20857 USA
[3] NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20962 USA
[4] Univ Connecticut, Sch Pharm, Storrs, CT 06269 USA
[5] Univ Connecticut, Inst Sci Mat, Storrs, CT 06269 USA
来源
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS | 1998年 / 59卷 / 02期
关键词
D O I
10.1016/S0952-3278(98)90089-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Analogs of arachidonylethanolamide (anandamide) were prepared to investigate the structural requirements for ligand binding to and activation of the CB1 and CB2 cannabinoid receptors. The importance of the presence and the placement of the carbonyl was examined with analogs lacking the carbonyl or with the carbonyl amide order reversed. The presence and location of the carbonyl is essential for high-affinity binding to both cannabinoid receptor subtypes, and for determination of signal transduction via G-proteins. Methyl groups were substituted on the 1'- and 2'-positions of arachidonylethanolamide and the significance of chirality was examined. Stereochemical differences in the ethanolamide group influence the affinity for both cannabinoid receptor subtypes and the signal transduction capabilities of the methanandamide derivatives.
引用
收藏
页码:111 / 118
页数:8
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