TTA-A2 was found to inhibit all three subtypes of low-voltage-gated T-type channels (CaV3.1, CaV3.2, and CaV3.3) with comparable potencies. Changing membrane resting potentials from −100 to −80 mV enhanced compound potency by ∼40-fold, from an IC50 of ∼4 μM to 0.1 μM, respectively, indicating state dependence of inhibition. in vivo studies have demonstrated that TTA-A2 reduces absence epilepsy seizures, pain perception, nicotine self-administration and weight gain. It also improves the quality of sleep and displays antipsychotic properties.
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