BRAIN PERMEABLE ZINC COMPLEX WITH NEUROPROTECTIVE ACTION

To establish a neuroprotective drug that readily permeates the cell me mbrane, the intracellular uptake, interaction with N-methyl-D-aspartat e receptors and protective activity against glutamate neuro toxicity o f several Zn-bis(thiosemicarbazone) complexes were investigated in the rodents. Among these Zn-bis(thiosemicarbazone) complexes, 2,3-butaned ione bis(N-4-dimethylthiosemicarbazonato) zinc complex (Zn-ATSM(2)) sh owed the highest brain uptake, indicating its prompt membrane permeabi lity. Receptor binding assays indicated that Zn-ATSM(2) elicited an in hibition potency of dizocilpine maleate binding to N-methyl-D-aspartat e receptors similar to that of Zn2+ ion. Moreover, Zn-ATSM(2) exhibite d promising effects against glutamate-induced neurotoxicity in the cul tured retinal neurons. These results suggest that Zn-ATSM, may serve a s a potential drug for the prevention of ischaemic neuronal damage, as it is highly membrane permeable and attenuates N-methyl-D-aspartate r eceptor mediated glutamate neurotoxicity in the rodents.