Effect of α-methyl- p-tyrosine on the incidence of spontaneous convulsions observed following barbital withdrawal

Abstract

Male Sprague-Dawley rats were made dependent on barbital by the administration of this drug in the drinking water following an established dosage regimen. Following abrupt barbital withdrawal, the incidence of convulsions was determined in barbital-dependent rats. Groups of these animals were treated with saline, 30, 60, 125 or 250 mg/kg α-methyl-para-tyrosine (αMPT) at the time of barbital withdrawal and a second time 16 hr later. A statistically significant (P < 0.01) dosage-related decrease in the incidence of withdrawal-related convulsions was observed in all of the αMPT-treated groups. Only the highest accumulative dosage of αMPT (500 mg/kg) produced any evidence of hypothermia. Pretreatment with the same dosages of αMPT did not affect pentylenetetrazol-induced convulsions indicating that αMPT in these concentrations possesses no general anticonvulsant properties. All of the dosages of αMPT utilized were capable of significantly decreasing whole brain levels of dopamine and noradrenaline, at least for a few hours. The results show that αMPT decreases the incidence of convulsions associated with barbital withdrawal and suggest that catecholamines may have a role in the manifestation of the barbiturate abstinence syndrome.