SYNTHESIS AND PHARMACOLOGICAL TESTING OF DEQUALINIUM ANALOG AS BLOCKERS OF THE APAMIN-SENSITIVE CA2-ACTIVATED K+ CHANNEL - VARIATION OF THELENGTH OF THE ALKYLENE CHAIN()

Dequalinium is a potent and selective blocker of the small conductance Ca2+-activated K+ (SKCa) channel in rat sympathetic neurones, Analogu es of dequalinium possessing 3-6, 8, 10, and 12 methylene groups in th e linking chain have been synthesized and tested for inhibition of the afterhyperpolarization in rat sympathetic neurones. The compounds hav ing a 5-12-carbon chain showed very little variation in their activity as SKCa channel blockers. The analogues possessing four and three met hylenes exhibited 3- and 8-fold lower potency, respectively, compared with dequalinium. These results are discussed in the context of possib le modes of binding of the compounds to the SKCa channel.