Phenobarbital

Valproate (VPA) is an anti-epileptic and mood-stabilizing drug with a broad range of action and which mechanism of action still remains in part elusive. Recently the discovery that VPA modifies the epigenome increasing the transcriptional rate of target genes raises the issue of understanding the exact role of this mechanism. In this work we tested the possibility that VPA could modify the epigenome of lymphomonocytes (PBMC) obtained from epileptic patients chronically treated in monotherapy with VPA and phenobarbital.

Methaqualone pretreatment for 3 or 6 days caused an induction of hepatic enzymes in the young male rat as measured by a reduction in hexobarbital-hypnosis. However, methaqualone pretreatment had no effect on the hexobarbital-hypnotic response in older male rats. Phenobarbital was a more potent enzyme inducer than methaqualone, and caused induction of liver enzymes in both age groups.

The effect of methaqualone on the induction of hepatic enzymes was evaluated in rats and compared with that of phenobarbital by measuring effects on hexobarbital and methaqualone hypnosis, plasma and tissue levels of methaqualone, hepatic aniline hydroxylase and aminopyrine demethylase activity and warfarin-induced hypoprothrombinemia. Maximal reductions in hexobarbital hypnosis occurred 3 days after daily administration of 60 mg of methaqualone per kg per day.

Four pharmacologic actions of intravenous ketamine (30 mg/kg) were studied in the rat. To elucidate the mechanism(s) terminating the pharmacologic effects, animals were pretreated with ketamine and agents anticipated to modify hepatic microsomal metabolism, including phenobarbital and SKF 525A.

The presence and mechanism of synergism of action between ethanol and amylobarbitone, phenobarbitone or methaqualone was determined by application of simple pharmacokinetic models to log dose-response curves and plasma concentration-time curves for the hypnotics alone or when ethanol was given concurrently. For all three hypnotics, ethanol was found to increase the duration of hypnosis, but the mechanism of action was different for each.

Chronic intracerebroventricular injection of phenobarbital results in the development of tolerance to the depressant effects of the drug. The neurotransmitters involved and the manner in which cerebral neurons adapt to this depressant effect are at present unknown. This study examines whether brain serotonin containing neurons participate in the attenuation of the hypnotic response caused by chronic barbiturate administration.