The novel anticonvulsant lamotrigine prevents dopamine depletion in C57 black mice in the MPTP animal model of Parkinson's disease.
The effect of the novel anticonvulsant Lamotrigine (LTG) was studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in C57BL/6 mouse brain. Whole brain dopamine levels were measured by HPLC-ED 2 days after treatment with MPTP (15 mg/kg s.c.). While LTG alone had no direct effect on dopamine levels at two hours or two days after treatment, MPTP induced dopamine depletion was significantly less in mice pretreated with LTG (approximate ED50: 6 mg/kg). LTG (38 mg/kg) was shown to completely protect against dopamine depletion 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 the 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 novel mechanism.
Jones-Humble
S A
SA
Wellcome Research Laboratories, Department of Pharmacology, Research Triangle Park, NC 27709.
Morgan
P F
PF
Cooper
B R
BR
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000077213:Lamotrigine; D020267:MPTP Poisoning; D051379:Mice; D008810:Mice, Inbred C57BL; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; D000077213:Lamotrigine; D004298:Dopamine