A new negative allosteric modulator, AP14145, for the study of small conductance calcium-activated potassium (KCa 2) channels.

AP14145 is a negative allosteric modulator of KCa 2.2 and KCa 2.3 channels that shifted the calcium dependence of channel activation, an effect strongly dependent on two identified amino acids. AP14145 prolonged AERP in rats and did not trigger any acute CNS effects in mice. The understanding of how KCa 2 channels are inhibited, at the molecular level, will help further development of drugs targeting KCa 2 channels.