Influence of antidepressant drugs on seizure susceptibility and the anticonvulsant activity of valproate in mice.

The tricyclic antidepressants, amitriptyline (20-30 mg/kg, i.p.) and imipramine (30-40 mg/kg), provided a significant protection against electro-convulsions (12 mA, 0.2 s stimulus duration) but desipramine (up to 40 mg/kg) remained ineffective. On the other hand, all drugs, amitriptyline (10 mg/kg), desipramine (20 mg/kg), and imipramine (20 mg/kg) distinctly potentiated the protective efficacy of valproate against maximal electroshock, reducing its ED 50 values from 255 mg/kg to 150, 135, and 128 mg/kg, respectively. In one case the plasma valproate level was measured and it was evident that desipramine (20 mg/kg) did not affect the plasma level of this antiepileptic.