Pharmacodynamic and pharmacokinetic interactions between alpha-methylparatyrosine and phenobarbitone

The hypnosis and hypothermia induced by phenobarbitone (100 mg/kg i.p.) were greatly potentiated by combined treatment with alpha-methylparatyrosine (alpha-MPT, 250 mg/kg i.p.). alpha-MPT per se produced sedation and hypothermia. Measurement of blood and brain levels of phenobarbitone in rats treated with phenobarbitone alone or phenobarbitone plus alpha-MPT revealed that the latter delayed the disappearance rates of phenobarbitone from both brain and plasma. These results suggest an interaction at the site of distribution, metabolism and/or excretion of phenobarbitone. The possibility of a pharmacodynamic interaction involving neurotransmitters is also discussed.