Barbiturate withdrawal and magnesium deficiency in mice.

C57BL/6J male mice rendered physically dependent on phenobarbital exhibited significantly lower whole-brain and serum-magnesium concentrations than did control mice. The symptoms of phenobarbital withdrawal were remarkably similar to those seen in magnesium-deficient mice exposed to a low-magnesium diet without drug exposure. These findings suggest that brain magnesium deficits produced by chronic phenobarbital withdrawal could contribute to the observed phenobarbital withdrawal syndrome. Administration of MgSO4 during withdrawal significantly reduced the incidence of tonicclonic and lethal tonic seizures.