CARBAMOYLATION OF BRAIN GLUTAMATE RECEPTORS BY A DISULFIRAM METABOLITE

S-Methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO), a metabolite of the drug disulfiram, is a selective carbamoylating agent for sulfh ydryl groups, Treatment of glutamate receptors isolated from mouse bra in with DETC-MeSO blocks glutamate binding, In vivo, carbamoylated glu tathione, administered directly to mice or formed by reaction of DETC- MeSO with glutathione in the blood, also blocks brain glutamate recept ors, Carbamoyl groups appear to be delivered to brain glutamate recept ors or to liver aldehyde dehydrogenase in vivo by a novel glutathione- mediated mechanism. Seizures caused by the glutamate analogs N-methyl- D-aspartate and methionine sulfoximine, or by hyperbaric oxygen, are p revented by DETC-MeSO, indicating that carbamoylation of glutamate rec eptors gives an antagonist effect, These observations offer an explana tion for some of the previously reported neurological effects of disul firam, such as its ability to prevent O-2-induced seizures, Furthermor e, some of the physiology of the disulfiram-ethanol reaction, that cou ld not be accounted for based on the known inhibition of aldehyde dehy drogenase alone, may be explained by disulfiram's effect on glutamate receptors.