CB2 cannabinoid receptor agonists:: pain relief without psychoactive effects?

被引:174
作者
Malan, TP [1 ]
Ibrahim, MM
Lai, J
Vanderah, TW
Makriyannis, A
Porreca, F
机构
[1] Univ Arizona, Dept Anaesthesiol, Tucson, AZ 85724 USA
[2] Univ Arizona, Dept Pharmacol, Tucson, AZ 85724 USA
[3] Univ Connecticut, Dept Med Chem, Storrs, CT 06269 USA
[4] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA
关键词
D O I
10.1016/S1471-4892(02)00004-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cannabinoid receptor agonists significantly diminish pain responses in animal models; however, they exhibit only modest analgesic effects in humans. The relative lack of efficacy in man may be because of the dose limitations imposed by psychoactive side effects. Cannabinoid agonists that selectively target CB2 (peripheral) cannabinoid receptors should be free of psychoactive effects, perhaps allowing for more effective dosing. CB2 receptor activation inhibits acute, inflammatory and neuropathic pain responses in animal models. In preclinical studies, CB2 receptor agonists do not produce central nervous system effects. Therefore, they show promise for the treatment of acute and chronic pain without psychoactive effects.
引用
收藏
页码:62 / 67
页数:6
相关论文
共 42 条
[1]   THE PERIPHERAL CANNABINOID RECEPTOR - ADENYLATE-CYCLASE INHIBITION AND G-PROTEIN COUPLING [J].
BAYEWITCH, M ;
AVIDORREISS, T ;
LEVY, R ;
BARG, J ;
MECHOULAM, R ;
VOGEL, Z .
FEBS LETTERS, 1995, 375 (1-2) :143-147
[2]   NGF but not NT-3 or BDNF prevents the A fiber sprouting into lamina II of the spinal cord that occurs following axotomy [J].
Bennett, DLH ;
French, J ;
Priestley, JV ;
McMahon, SB .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1996, 8 (04) :211-220
[3]   CANNABINOID-RECEPTOR EXPRESSION IN HUMAN-LEUKOCYTES [J].
BOUABOULA, M ;
RINALDI, M ;
CARAYON, P ;
CARILLON, C ;
DELPECH, B ;
SHIRE, D ;
LEFUR, G ;
CASELLAS, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 214 (01) :173-180
[4]   Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor [J].
Buckley , NE ;
McCoy, KL ;
Mezey, É ;
Bonner, T ;
Zimmer, A ;
Felder, CC ;
Glass, M ;
Zimmer, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2000, 396 (2-3) :141-149
[5]   Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide [J].
Calignano, A ;
La Rana, G ;
Piomelli, D .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 419 (2-3) :191-198
[6]   Control of pain initiation by endogenous cannabinoids [J].
Calignano, A ;
La Rana, G ;
Giuffrida, A ;
Piomelli, D .
NATURE, 1998, 394 (6690) :277-281
[7]  
Campbell FA, 2001, BMJ-BRIT MED J, V323, P1
[8]   CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain [J].
Clayton, N ;
Marshall, FH ;
Bountra, C ;
O'Shaughnessy, CT .
PAIN, 2002, 96 (03) :253-260
[9]  
Daemen M, 1998, Acta Orthop Belg, V64, P441
[10]  
Daemen MARC, 1998, NEUROL RES, V20, P41