INHIBITION BY IMIDAZOLINE AND IMIDAZOLIDINE DERIVATIVES OF GLIBENCLAMIDE-SENSITIVE K-OOCYTES( CURRENTS IN XENOPUS)

The effects of imidazoline and imidazolidine derivatives on glibenclam ide-sensitive K+ currents induced by the novel K+ channel opener, Y-26 763 no-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol), were investigat ed in voltage-clamped follicle-enclosed Xenopus oocytes. Of 14 imidazo line derivatives and seven imidazolidine derivatives tested, phentolam ine, (-)-cibenzoline, (+)-cibenzoline, alinidine, oxymetazoline, antaz oline, midaglizole, xylometazoline, tramazoline and ST91 (2-(2,6-dieth ylphenylamino)-2-imidazolin hydrochloride) potently suppressed Y-26763 -induced K+ currents (IC50 < 80 mu M). The compounds which lack an aro matic ring in their structure, 2-methyl-2-imidazole and 2-hydrazino-2- imidazoline, did not affect the K+ currents. Clonidine and idazoxan, w hich both bind to imidazoline-preferring binding sites with high affin ity in various tissues, showed only a small inhibitory effect on Y-267 63-induced K+ currents (IC50 780 mu M and 955 mu M, respectively). The non-imidazoline/non-imidazolidine alpha-adrenoceptor antagonists, WB- 4101 (2-(2,6-dimethoxy-phenoxy ethyl)-aminomethyl-1,4-benzodioxane hyd rochloride), yohimbine and rauwolscine, showed suppressive effects on Y-26763-induced K+ currents (IC50, 203 mu M, 813 mu M and 832 mu M, re spectively). Octopamine (1 mM), a non-imidazoline/non-imidazolidine al pha-adrenoceptor agonist, was inactive. The results suggest that (1) a n aromatic ring or aromatic rings are an essential moiety for imidazol ine or imidazolidine derivatives to block glibenclamide-sensitive K+ c urrents in oocytes, and (2) the K+ current-blocking ability of imidazo lines and imidazolidines is related to the alkylation of the benzene r ing and the existence of a tertiary amine structure. The K+ current-bl ocking effects of imidazolines or imidazolidines may not be mediated b y alpha-adrenoceptors, at least in follicle-enclosed Xenopus oocytes.