TTA-A2

Low-voltage-activated (T-type/Ca_V3) Ca²⁺ channels are a subclass of voltage-dependent Ca²⁺ channels allowing Ca²⁺ entry near the resting potential of most cells¹. Various synthetic T-channel blockers have been described in the past few years including TTA-A2, a potent, state-dependent, and highly selective T-type Ca_V antagonist².

TTA-A2 was found to inhibit all three subtypes of low-voltage-gated T-type channels (Ca_V3.1, Ca_V3.2, and Ca_V3.3) with comparable potencies. Changing membrane resting potentials from −100 to −80 mV enhanced compound potency ∼40-fold, from an IC₅₀ of ∼4 μM to 0.1 μM, respectively, indicating state dependence of inhibition³. in vivo studies have demonstrated that TTA-A2 reduces absence epilepsy seizures⁴, pain perception⁵, nicotine self-administration⁶ and weight gain⁷. It also improves the quality of sleep⁷ and displays antipsychotic properties⁸.