The effect of diphenylhydantoin on brain 5-hydroxytryptamine metabolism and function

Abstract

Diphenylhydantoin (DPH; 75 mg/kg) administration to rats, enhanced the hyperactivity syndrome which results from increased brain 5-hydroxytryptamine (5-HT) synthesis produced by the injection of tranylcypromine (20 mg/kg) and l-tryptophan (100 mg/kg). One dose of DPH alone had no effect on 5-HT synthesis and did not enhance the hyperactivity resulting from administration of the suggested 5-HT agonist 5-methoxy- N, N-dimethyltryptamine. This argues against DPH altering acutely the postsynaptic responses to released 5-HT. Administration of DPH (75 mg/kg) twice daily for 2 days increased the rate of 5-HT synthesis by 100%. Chlorimipramine (25 mg/kg), which inhibits 5-HT re-uptake, also enhanced the hyperactivity but decreased 5-HT synthesis by 50% when given on the same regimen. This suggests that DPH is not altering 5-HT re-uptake. Anti-epileptic drugs structurally similar to DPH did not potentiate the hyperactivity syndrome. It is suggested that DPH alters the amount of 5-HT that is released and is active at the nerve ending. The apparent similarities in action between lithium and DPH on 5-HT function and metabolism are noted and a possible common mechanism of action suggested.