TTA-A2 is a potent, selective and orally active T-type voltage gated calcium channel antagonist that reduces the activation of PXR. TTA-A2 is equally effective on Cav3.1 (a1G) and Cav3.2 (a1H) channels, with IC50 values of 89% and 89% at -80 and -100 mV holding potentials, respectively. The IC50 values at -80 and -100 mV holding potentials were 89 nM and 92 nM, respectively. TTA-A2 can be used to study a variety of human neurological disorders, including sleep disorders and epilepsy[1][2].TTA-A2 exhibits high affinity in the α1I binding assay with an affinity of 1.2 nM, and has excellent selectivity for hERG potassium channels and L-type calcium channels (both with IC50 values greater than 10 μM)[1].
TTA-A2 动物研究
Animal study
Administered orally as a single dose at 3 mg/kg, TTA-A2 significantly altered sleep architecture in rats. Shortly after drug administration, rats showed a decrease in active wake, along with an increase in delta sleep and a decrease in rapid eye movement sleep. Furthermore, these effects lasted for up to 4 hours after drug administration in rats[1].At a dose of 10 mg/kg, administered orally once daily for 5 days, TTA-A2 had selective effects on recurrent activity in the thalamocortical network. TTA-A2 can inhibit active wake and promote slow-wave sleep in wild-type mice, but cannot inhibit active wake and slow-wave sleep in mice lacking both Cav3.1 and Cav3.3[2].
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