CyPPA, a subtype-selective positive modulator of SK channels, decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization.
CyPPA, a positive modulator of SK2 and SK3, reduces the activity of dopaminergic neurons and inhibits dopamine release with EC50 values of 14 μM and 5.6 μM, repectively. CyPPA counteracts hyperdopaminergic behaviors induced by methylphenidate.
In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. CyPPA induces a concentration-dependent increase in the apparent Ca2+ sensitivity of channel activation, changing the EC50 (Ca2+) from 429 nM to 59 nM