Cannabinoid receptor agonists

In terms of chemical structure, established cannabinoid receptor agonists fall essentially into four main groups classical, nonclassical, aminoalkylindole and eicosanoid (reviewed in Howlett et al. 2002 Pertwee 1999a). 

3-( 1I -dimethy l-cycloh exyl )-A -TH C Fig. 4. The structures of five synthetic dassical cannabinoids 

Nonclassical cannabinoids consist of bicyclic and tricyclic analogues of A -THC that lack a pyran ring examples include CP55940, CP47497, CP55244 and HU-308 (Fig. 6). They are, therefore, closely related to the classical cannabinoids. 

Members of the eicosanoid group of cannabinoid receptor agonists have markedly different structures both from the aminoalkylindoles and from classical and nonclassical cannabinoids. Important members of this group are the endocannabinoids, arachidonoylethanolamide (anandamide), 0-arachidonoylethan-olamine (virodhamine), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl 

Several cannabinoid receptor agonists bind more or less equally well to CBi and CB2 receptors (Table 2), although they do exhibit different relative intrinsic activities at these receptors. Among these are HU-210, CP55940, lt-(-i-)-WlN55212, (-)-A -THC, anandamide and 2-arachidonoyl glycerol (reviewed in Howlett et al. 2002 Pertwee 1999a). 

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Braida D, Pozzi M, Cavallini R, et al Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat interaction with the opioid system. EurJ Pharmacol 413 227-234, 2001... 

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As outlined earlier, anandamide was the first among the endogenous cannabinoid receptor agonists to be identified. It exhibits higher binding affinity for the CBi receptor Ki — 89 nM) than for the CB2 receptor (il = 371 nM) [81]. Anandamide has typical cannabinoid activities including decreased spontaneous motor activity, immobility and production of hypothermia and analgesia [147, 148]. However, this action in vivo is of shorter duration than... 

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Cannabinoid receptors include the CB1 receptors (which have a high incidence in the CNS and inhibit adenylyl cyclase, close Ca2+ channels and open K+ channels via Gai) and CB2 receptors (which are present in immune cells and act via Gai proteins to inhibit adenylyl cyclase). CB1 and CB2 receptors bind the endogenous ligand anandamide (arachi-donylethanolamide) as well as A9-tetrahydroc.annabinol from marijuana (Cannabis saliva). A9-Tetrahydroc,annabinol antagonizes the peripheral CB2 receptor but acts as an agonist for the CNS CB1 receptor. Cannabinoid receptor agonists have appetite stimulant and psychoactive effects and have therapeutic potential for relief from nausea and pain. 

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