The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced antinociception in rats.

The purported CB1 cannabinoid antagonist SR 141716A has proven to be a useful tool in the investigation of cannabinoid pharmacology. This antagonist was employed in the present study to investigate the antinociceptive and cataleptic effects of cannabinoids after either systemic or intracerebroventricular (ICV) administration. The antinociceptive potency of systemically administered delta 9-tetrahydrocannabinol (delta 9-THC) was decreased 18-fold by SR 141716A, from an ED50 value of 0.3-5.1 mg/kg. Similarly, it completely blocked the antinociceptive effects of delta 9-THC and CP 55,940, a potent bicyclic cannabinoid, after ICV administration. In addition, it prevented cannabinoid-induced catalepsy when given by either route of administration. In contrast, SR 141716A failed to antagonize the antinociceptive effects of morphine, indicating its selectivity for cannabinoid receptors. These findings indicate that the antinociceptive and cataleptic effects of delta 9-THC and CP 55,940 are mediated through CB1 cannabinoid receptors.