PREVENTION BY A GINKGO-BILOBA EXTRACT (GBE-761) OF THE DOPAMINERGIC NEUROTOXICITY OF MPTP

Abstract— In mice implanted subcutaneously with osmotic minipumps releasing the neurotoxic agent N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 7 days (105 μg h−1/mouse) (∼ 100 mg kg−1 day−1) a significant reduction (∼ 25%) in the striatal dopaminergic nerve endings was observed. This neurotoxic effect was prevented by the semi‐chronic ingestion of a Ginkgo biloba extract for 17 days (GBE 761, ∼ 100 mg kg−1 day−1). The high concentrations (∼ 1 g L−1) at which GBE 761 in‐vitro either prevented the uptake of [3H]dopamine by synaptosomes prepared from striatum, or prevented the specific binding of the pure dopamine uptake inhibitor [3H]GBR 12783 to membranes prepared from striatum suggests that the prevention of the MPTP neurotoxicity does not depend on an inhibition of the MPTP uptake by dopamine neurons. This is also suggested by the lack of prevention of the in‐vitro striatal binding of [3H]GBR 12783 administered i.v. at a tracer dose, in mice pretreated for 8 days with GBE 761 (100 mg kg−1 p.o.) and receiving a supplementary gastric administration of GBE 761 (100 mg kg−1) 1 h before testing. Similar treatment with GBE 761 did not modify the toxicity for dopamine neurons of 6‐hydroxydopamine (20 μg) directly injected into the striatum of rats. 1990 Royal Pharmaceutical Society of Great Britain