Z944 is a highly selective (70 fold over N-type) T-type calcium channel blocker (IC50 hCav3.2 = 50 nM).1 It was 2.5 to 4-fold more potent for the inactivated T-type channel than for the closed channel. It was also selective against the Cav1.2, hERG, and Nav1.5 channels. Z944 potently suppressed seizures in absence epilepsy1 and temporal lobe epilepsy2 models. It reversed thermal hyperalgesia and conditioned place preference in a neuropathic pain model.3 Z944 reversed mechanical allodynia in a model of persistent inflammatory pain4 and displayed an antihyperalgesic effect in a model of trigeminal neuralgia5. Z944 significantly improved autism spectrum disorder-related behaviors via suppression of reticular thalamic hyperexcitability.6
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