202W92

202W92 is a small molecule sodium channel inhibitor and a structural analog of the anticonvulsant lamotrigine. Developed by Glaxo Wellcome (now GSK), the compound was investigated for its potential neuroprotective effects in Parkinson's disease. Its primary mechanism of action involves the potent blockade of voltage-gated sodium channels, which leads to the inhibition of glutamate release—a process thought to contribute to neuronal damage and excessive glutamatergic activity in Parkinson's. Preclinical studies have demonstrated that 202W92 is more selective than related compounds like riluzole and lamotrigine, as it does not significantly affect N-type or P/Q-type calcium channels. In dopaminergic neurons, it has been shown to inhibit spontaneous action potential firing and reduce the frequency of both excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) without affecting postsynaptic receptor responses.