title: Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the responses of isolated canine arteries.
abstract: The effects of NKY-722 ((+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0), a new water soluble dihydropyridine derivative on the responses of isolated canine arteries were examined. NKY-722 (IC50: 5-16 x 10(-10) mol/l), nicardipine (IC50: 5-10 x 10(-10) mol/l) and nifedipine (IC50: 44-195 x 10(-10) mol/l) relaxed four arteries in the potency order of basilar > coronary > mesenteric > intrarenal arteries. NKY-722 was nearly equipotent to nicardipine and about 10 times more potent than nifedipine. [3H]NKY-722 was accumulated in the four arteries in the same order of amount as the vasoinhibitory effect. All three drugs inhibited the contraction induced by Ca2+ and methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylophenyl)-p yri dine-5- carboxylate (Bay K 8644) in the mesenteric arteries, indicating their Ca2+ antagonistic actions. NKY-722 and nicardipine were nearly equipotent and about 100 times more potent than nifedipine on the Ca(2+)-induced contraction and was about 4 times more potent than nicardipine and 400 times more potent than nifedipine on the Bay K 8644-induced contraction. NKY-722, nicardipine and nifedipine relaxed the mesenteric arteries precontracted with KCl by more than 90%, while they relaxed the arteries contracted with PGF2 alpha, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-PGF2 alpha (U-46619) and endothelin-1 only by 40-70%. The IC50 values of NKY-722 and nicardipine were similar and much smaller than that of nifedipine for all four contracting agents.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kanda
authors.forename: H
authors.initials: H
authors.lastname: Shirahase
authors.forename: K
authors.initials: K
authors.lastname: Kurahashi
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: F
authors.initials: F
authors.lastname: Fukata
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C058351:NKY 722; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine