Effect of beta-myrcene on pentobarbital sleeping time

Evidence that beta-myrcene (MYR) interferes with the metabolic activation of premutagens has been provided by in vitro studies. In order to determine whether MYR also interferes with the in vivo metabolism of xenobiotics, thereby modifying pharmacological responses to drugs, we investigated the effects of this monoterpene on pentobarbital (PT) sleeping time in rats. Two experiments were carried out. In the first, a single dose of MYR (0.25, 0.5 or 1.0 g/kg po) was given 1 h before PT (40 mg/kg ip). No effect was observed with the two lowest doses, but the highest MYR dose given 1 h before PT increased the PT-induced sleeping time (131 +/- 15 min vs 64 +/- 15 min for controls, mean +/- SD). In the second experiment, male rats were treated with MYR (1.0 g/kg po once a day) for 14 days and injected with PT (40 mg/kg ip) 24 h after the last dose of MYR. Repeated treatment with MYR markedly reduced PT sleeping time compared to the vehicle-treated control group (21 +/- 13 min vs 35 +/- 19 min for controls, mean +/- SD). These results indicate that MYR interferes with the in vivo barbiturate metabolism and support the view that MYR induces the phenobarbital-inducible cytochrome P-450 (P-450 2B subfamily) enzymes in the rat.