Biological Activity |
Mirogabalin besylate is a selective and orally available ligand for the alpha2delta subunit of voltage-gated calcium channels, with Kds of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human alpha2delta-1, human alpha2delta-2, rat alpha2delta-1, and rat alpha2delta-2, respectively. IC50 & Target: Kd: 13.5 nM (Human alpha2delta-1), 22.7 nM (Human alpha2delta-2), 27 nM (Rat alpha2delta-1), 47.6 nM (Rat alpha2delta-2)[1] In Vitro: Mirogabalin besylate is a ligand for the alpha2delta subunit of voltage-gated calcium channels, with Kds of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human alpha2delta-1, human alpha2delta-2, rat alpha2delta-1, and rat alpha2delta-2, respectively. Mirogabalin shows binding affinity for the gabapentin binding site in rat cortical brain homogenates with the IC50 value of 16.0 nM. Mirogabalin has no effect on any other receptors, channels, transporters, or enzymes at 50 uM[1]. In Vivo: Mirogabalin besylate (3 and 10 mg/kg) markedly increases AUC0-8 hours values in a dose-dependent manner in partial sciatic nerve ligation model rats. Mirogabalin (2.5, 5, and 10 mg/kg) causes significant and dose-dependent increase in AUC0-12 hours values and enhances analgesic effects, with estimated ED50 of 4.4, 3.1, and <2.5 mg/kg on day 1, day 3, and day 5, respectively. Moreover, Mirogabalin besylate shows no obvious effect on rota-rod performance and locomotor activity at 3 and 10 mg/kg via oral administration, exhibits significant inhibition on rota-rod performance at 10, 30, and 100 mg/kg, and decreases locomotor activity at 30 and 100 mg/kg in rats[1]. |