Chlorpromazine and related phenothiazines inhibit the ATP-sensitive K+ channel.

Whole-cell, current clamp, single channel recordings and 86Rb+ flux techniques were used to show that phenothiazines inhibit ATP-sensitive K+ channels (KATP) in HIT-T15 beta-cells. Chlorpromazine inhibition was observed when KATP channels were activated by ATP depletion or by direct treatment with a classical KATP channel opener, diazoxide. The order of potency of the phenothiazines tested was chlorpromazine greater than triflupromazine greater than fluphenazine greater than trifluopromazine with IC50 values of 1, 4, 6 and 20 microM, respectively. The inhibition was reversible.