ABSTRACT
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
Subject(s)
Animals , Male , Rats , Pentobarbital/antagonists & inhibitors , Sleep/drug effects , Terpenes/pharmacology , Cytochrome P-450 Enzyme System/biosynthesis , Enzyme Induction , Pentobarbital/metabolism , Rats, Wistar , Terpenes/administration & dosageSubject(s)
Analgesia , Animals , Appetite/drug effects , Blood Pressure/drug effects , Cats , Central Nervous System/drug effects , Central Nervous System Stimulants/pharmacology , Diuresis/drug effects , Dogs , Female , Guinea Pigs , Male , Mice , Muscle Contraction/drug effects , Myocardial Contraction/drug effects , Pentobarbital/antagonists & inhibitors , Piperazines/pharmacology , Rabbits , Rats , Reflex/drug effects , Reserpine/antagonists & inhibitors , Synaptic Transmission/drug effects , Uterine Contraction/drug effectsABSTRACT
The uterotropic effect of clofibrate and phenylbutazone was studied in immature female rats. A significant increase in the uterine wet weight was observed following clofibrate and phenylbutazone administration. Clofibrate but not phenylbutazone synergized with the uterotropic effect of ethinyl-oestradiol. Phenylbutazone pretreatment significantly decreased the pentobarbitone sleeping time. The uterotropic effect of clofibrate and phenylbutazone might involve displacement of 17-beta oestradiol (or ethinyl oestradiol) from plasma albumin binding sites in rats.
Subject(s)
Animals , Clofibrate/pharmacology , Drug Synergism , Estrogens , Ethinyl Estradiol/pharmacology , Female , Organ Size/drug effects , Pentobarbital/antagonists & inhibitors , Phenylbutazone/pharmacology , Rats , Sleep/drug effects , Uterus/drug effectsABSTRACT
The interaction of pentobarbitone sodium with three analeptics viz. micoren, pentylenetetrazol and methedrine was studied in mice. Micoren prolonged pentobarbitone sleeping time. pentylenetetrazol shortened the sleeping time. Methedrine also shortened the sleeping time, but clonic convulsions of mild to severe intensity were noticed 45-60 minutes after the drug injection.