ASP2905

ASP2905 is an inhibitor of voltage-gated potassium channel K_v12.2.¹ It inhibits potassium currents in CHO cells expressing K_v12.2 (IC₅₀ = 9 nM). ASP2905 is selective for K_v12.2 over 55 transmembrane proteins at 10 µM. It reduces the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) in primary rat hippocampal neurons when used at concentrations of 0.1 and 1 µM. ASP2905 increases dopamine and acetylcholine efflux in the rat medial prefrontal cortex and improves latent learning in the water-finding task in mice.² It also reduces hyperlocomotion induced by phencyclidine (PCP) in mice when administered at doses of 0.03, 0.1, and 0.3 mg/kg and reduces PCP-induced increases in immobility in mice in the forced swim test at 0.01 and 0.1 mg/kg.³

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1. Takahashi, S., Inamura, K., Yarimizu, J., et al. Neurochemical and neuropharmacological characterization of ASP2905, a novel potent selective inhibitor of the potassium channel KCNH3. Eur. J. Pharmacol. 810, 26-35 (2017).

2. Takahashi, S., Ohmiya, M., Honda, S., et al. The KCNH3 inhibitor ASP2905 shows potential in the treatment of attention deficit/hyperactivity disorder. PLoS One 13(11), e0207750 (2018).

3. Takahashi, S., Okamura, A., Yamazaki, M., et al. ASP2905, a specific inhibitor of the potassium channel K_v12.2 encoded by the Kcnh3 gene, is psychoactive in mice. Behav. Brain Res. 378:112315, (2020).