Calcium uptake mechanisms affected by some convulsant and anticonvulsant drugs.

An anticonvulsant (phenytoin) and a convulsant barbiturate (5-(2-cyclohexylidene ethyl)-5-ethyl-barbituric acid) (CHEB) reduced depolarization-coupled 45Ca uptake by synaptosomes from rat brain. CHEB reduced uptake to the level of undepolarized control samples. Phenobarbital failed to affect synaptosomal 45Ca uptake. Phenobarbital inhibited mitochondrial 45Ca uptake by 38%. CHEB was even more effective, lowering mitochondrial 45Ca uptake nearly to the levels induced by the mitochondrial inhibitors KCN, ruthenium red and dinitrophenol. Phenytoin, phenobarbital and CHEB did not affect ATP-dependent 45Ca uptake by the endoplasmic reticulum in lysed synaptosomes. In view of the effect of CHEB, a known convulsant, in limiting Ca uptake by depolarized synaptosomes, an effect which was greater than either that of phenytoin or phenobarbital, an identification of such a mechanism with anticonvulsant or sedative properties may be oversimplified.