Apparent CB1 Receptor Rimonabant Affinity Estimates
Grim, T. W., Morales, A. J., Thomas, B. F., Wiley, J. L., Endres, G. W., Negus, S. S., & Lichtman, A. H. (2017). Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model. Journal of Pharmacology and Experimental Therapeutics, 362(1), 210-218. DOI: 10.1124/jpet.117.240192
Synthetic cannabinoids (SCs) represent an emerging class of abused drugs associated with psychiatric complications and other substantial health risks. These ligands are largely sold over the internet for human consumption, presumably because of their high cannabinoid 1 receptor (CB1R) affinity and their potency in eliciting pharmacological effects similar to Delta(9)-tetrahydrocannabinol (THC), as well as circumventing laws illegalizing this plant. Factors potentially contributing to the increased prevalence of SC abuse and related hospitalizations, such as increased CB1R efficacy and non-CB1R targets, highlight the need for quantitative pharmacological analyses to determine receptor mediation of the pharmacological effects of cannabinoids. Accordingly, the present study used pA(2) and pK(B) analyses for quantitative determination of CB1R mediation in which we utilized the CB1R-selective inverse agonist/antagonist rimonabant to elicit rightward shifts in the dose-response curves of five SCs (i.e., A-834,735D; WIN55,212-2; CP55,950; JWH-073; and CP47,497) and THC in producing common cannabimimetic effects (i.e., catalepsy, antinociception, and hypothermia). The results revealed overall similarity of pA(2) and pK(B) values for these compounds and suggest that CB(1)Rs, and not other pharmacological targets, largely mediated the central pharmacological effects of SCs. More generally, affinity estimation offers a powerful pharmacological approach to assess potential receptor heterogeneity subserving in vivo pharmacological effects of SCs.