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 tonic-clonic and lethal tonic seizures.