Eur J Pharmacol 1994 Jul 11;2593:223-31. doi: 10.1016/0014-2999(94)90648-3.

Inhibition by imidazoline and imidazolidine derivatives of glibenclamide-sensitive K+ currents in Xenopus oocytes.

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The effects of imidazoline and imidazolidine derivatives on glibenclamide-sensitive K+ currents induced by the novel K+ channel opener, Y-26763 ((+)-(3S,4R)-4-(N-acetyl-N-benzyloxyamino)-6-cyano-3,4-dihydro-2,2 -dimethyl-2H-1-benzopyran-3-ol), were investigated in voltage-clamped follicle-enclosed Xenopus oocytes. Of 14 imidazoline derivatives and seven imidazolidine derivatives tested, phenotalmine, (-)-cibenzoline, (+)-cibenzoline, alinidine, oxymetazoline, antazoline, midaglizole, xylometazoline, tramazoline and ST91 (2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride) potently suppressed Y-26763-induced K+ currents (IC50 < 80 microM). The compounds which lack an aromatic ring in their structure, 2-methyl-2-imidazole and 2-hydrazino-2-imidazoline, did not affect the K+ currents. Clonidine and idazoxan, which both bind to imidazoline-preferring binding sites with high affinity in various tissues, showed only a small inhibitory effect on Y-26763-induced K+ currents (IC50 780 microM and 955 microM, respectively). The non-imidazoline/non-imidazolidine alpha-adrenoceptor antagonists, WB-4101 (2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride), yohimbine and rauwolscine, showed suppressive effects on Y-26763-induced K+ currents (IC50 203 microM, 813 microM and 832 microM, respectively). Octopamine (1 mM), a non-imidazoline/non-imidazolidine alpha-adrenoceptor agonist, was inactive. The results suggest that (1) an aromatic ring or aromatic rings are an essential moiety for imidazoline or imidazolidine derivatives to block glibenclamide-sensitive K+ currents in oocytes, and (2) the K+ current-blocking ability of imidazolines and imidazolidines is related to the alkylation of the benzene ring and the existence of a tertiary amine structure. The K+ current-blocking effects of imidazolines or imidazolidines may not be mediated by alpha-adrenoceptors, at least in follicle-enclosed Xenopus oocytes.

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