THE NOVEL ANTICONVULSANT LAMOTRIGINE PREVENTS DOPAMINE DEPLETION IN C57 BLACK MICE IN THE MPTP ANIMAL-MODEL OF PARKINSONS-DISEASE

The effect of the novel anticonvulsant Lamotrigine (LTG) was studied o n 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in C57BL/6 mouse brain. Whole brain dopamine levels were me asured by HPLC-ED 2 days after treatment with MPTP (15 mg/kg s.c.). Wh ile LTG alone had no direct effect on dopamine levels at two hours or two days after treatment, MPTP induced dopamine depletion was signific antly less in mice pretreated with LTG (approximate ED50: 6 mg/kg). LT G (38 mg/kg) was shown to completely protect against dopamine depletio n when given 1 or 2 hours prior to MPTP administration. The effect of LTG (38, 100 mg/kg) on MPTP toxicity was compared to the effects of th e anticonvulsants phenytoin (67 mg/kg), carbamazepine (156 mg/kg), and riluzole (33 mg/kg) and the Ca++ channel blocker nicardipine (0.1 mg/ kg). Only phenytoin and LTG showed significant protection against MPTP . Results suggest LTG prevents MPTP induced dopamine depletion via a n ovel mechanism.