Cannabinoid CB1/CB2 receptor

Brooks JW, Pryce G, Bisogno T, Jaggar SI, Hankey DJR, Brown P, Bridges D, Ledent C, Bifulco M, Rice ASC, Di Marzo V, Baker D (2002) Arvanil-induced inhibition of spasticity and persistent pain evidence for therapeutic sites of action different from the vanilloid VRl receptor and cannabinoid CB1/CB2 receptors. Eur J Pharmacol 439 83-92... 

Both cannabinoid CB1/CB2 receptor agonists (A -THC [Dronabinol] and nabilone [Cesamet]) and selective cannabinoid CBi receptor antagonists (e.g., SR141716A [Rimonabant]) can be clinically used to respectively increase and decrease appetite (1). 

Spencer and coworkers reported the domino synthesis of 11 examples of 2-substituted-5-aminooxazole-4-carbonitriles 44 in 71-96% yields by microwave-mediated and flow chemistry (Scheme 12.16). Modifications around the oxazole motif could be made at positions 2, 4, and 5, aSbrding a number of rule of three fragments. They obtained three oxazoles, which showed micromolar Ki values against cannabinoid (CB1/CB2) receptors [37]. 

Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Mitchell RL. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 1995 48 443-449. 

Jarai Z, Wagner J, Varga K, Lake KD, Compton, DR, Martin BR, Zimmer AM, Bonner Tl, Buckley NE, Mezey E, Rajdan RK, Zimmer A, Kunos G. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct form CB1 or CB2 receptors. Proc Natl Acad Sci USA 1999 96 14136-14141. 

Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997 74 129-180. 

Anandamide was isolated from water-insoluble fractions of the porcine brain. It binds to CB1 with rather moderate affinity (Ki 61 nM) and a low affinity for the CB2 receptor (Ki 1930 nM). The name anandamide is based on its chemical nature (an amide) and the Sanskrit word ananda meaning bliss. The chemical structure of anandamide can be divided into two major molecular fragments a polar ethanolamido head group and a hydrophobic arachidonyl chain. The polar head group comprises a secondary amide functionality with an N-hydroxyalkyl substituent while the lipophilic fragment is a non-conjugated c/ s tetraolefinic chain and an n-pentyl chain reminiscent of the lipophilic side chain found in the classical cannabinoids. A number of anandamide analogs have been synthesized and demonstrated to have considerable selectivity for the CB1 receptor in comparison to the CB2 receptor. 

However A9-tetrahydrocannabinol anatagonizes the peripheral CB2 receptor while acting as an agonist for the CNS CB1 receptor [133]. Cannabinoid receptors mediate the appetite stimulant and psychoactive effects of cannabinoids which have therapeutic potential for relief from nausea and pain [132]. 

Rahn, E. J., Makriyannis, A., and Hohmann, A. G. (2007). Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in... 

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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