RT Journal Article
SR Electronic
T1 The Effect of the Enzyme Inhibitor Phenylmethylsulfonyl Fluoride on the Pharmacological Effect of Anandamide in the Mouse Model of Cannabimimetic Activity
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1138
OP 1143
VO 283
IS 3
A1 David R. Compton
A1 Billy R. Martin
YR 1997
UL http://jpet.aspetjournals.org/content/283/3/1138.abstract
AB Anandamide is an putative endogenous cannabinoid ligand that produces pharmacological effects similar to those of Δ9-tetrahydrocannabinol, the principle psychoactive constituent in marijuana. There is considerable evidence that the enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF) is capable of altering the actions of anandamide in vitro by blocking its metabolism. Therefore, studies were conducted in mice to determine whether PMSF could produce cannabinoid effects by altering endogenous levels of anandamide as well as determining whether PMSF could potentiate the effects of exogenously administered anandamide. Mice receiving i.p. injections of PMSF exhibited cannabinoid effects that included antinociception, hypothermia and immobility with ED50 values of 86, 224 and 206 mg/kg, respectively. Spontaneous activity was reduced at doses greater than 100 mg/kg. However, none of these effects was blocked by the cannabinoid antagonist SR 141716A. On the other hand, pretreatment with an inactive dose of PMSF (30 mg/kg) potentiated the effects of anandamide on tail-flick response (antinociception), spontaneous activity and mobility by 5-, 10- and 8-fold, respectively. PMSF did not alter anandamide’s hypothermic effects. Overall, these findings with PMSF underscore the importance of metabolism in the actions of anandamide. It still must be established whether metabolites of anandamide contribute to its pharmacological activity. The American Society for Pharmacology and Experimental Therapeutics