Detail of "75695-93-1"

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PN 200-110, a new calcium antagonist: electrophysiological, inotropic, and chronotropic effects on guinea pig myocardial tissue and effects on contraction and calcium uptake of rabbit aorta

PN 200-110, a new calcium antagonist: electrophysiological, inotropic, and chronotropic effects on guinea pig myocardial tissue and effects on contraction and calcium uptake of rabbit aorta. Hof, R. P.; Scholtysik, G.; Loutzenhiser, R.; Vuorela, H. J.; Neumann, P. (Cardiovasc. Unit Preclin. Res., Sandoz Ltd., Basel, Switz.). J. Cardiovasc. Pharmacol., 6(3), 399-406 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Action potentials in guinea pig papillary muscles were changed little by PN 200-110 (I) [75695-93-1], 10-7 M, except for a slight shortening of the duration of the plateau phase. Slow-action potentials elicited in partially depolarized papillary muscles were gradually diminished and finally blocked by this concn. of PN; contractile force was diminished in normal and partially depolarized muscles. The rate of spontaneously beating guinea pig right atria was decreased dose dependently (EC25 4.5 ′ 10-10 M). The EC25 for the neg. inotropic effects measured on paced guinea pig left atria was 1.5 ′ 10-8 M. No membrane-stabilizing effects were found. Ca2+-induced contraction of rabbit aorta in depolarizing bath soln. was inhibited with an apparent pA2 of 10.3. Contraction elicited by graded depolarization at a const. Ca2+ concn. was inhibited with an EC50 of 1.4 ′ 10-9 M. Under resting conditions PN did not alter net uptake of 45Ca2+. KCl-stimulated uptake was inhibited with an EC50 of 3.6 ′ 10-9 M. Neither noradrenaline-induced contractions nor noradrenaline-stimulated net uptake of 4Ca2+ were inhibited by a concn. of PN as high as 10-5 M. Thus, PN is selective on cardiac tissue with respect to neg. chronotropic vs. inotropic activity and on rabbit aorta with respect to potential-operated vs. receptor-operated channels.

Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anesthetized cats and dogs

Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anesthetized cats and dogs. Hof, R. P.; Hof, A.; Scholtysik, G.; Menninger, K. (Cardiovasc. Unit Preclin. Res., Sandoz Ltd., Basel, Switz.). J. Cardiovasc. Pharmacol., 6(3), 407-16 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of PN 200-110 (PN)(I) [75695-93-1] on the cardiovascular system were investigated in chloralose-urethane-anesthetized cats. PN decreased blood pressure (BP) and heart rate (HR) and increased cardiac output (CO) and total peripheral resistance dose dependently after i.v. doses of 1-10 mg/kg. Regional blood flow changes effected by an i.v. dose of 10 mg/kg were measured with microspheres. Flow to the heart, brain, and skeletal muscle increased selectively, and intramyocardial flow was redistributed in favor of the left ventricular subepicardial layer. The bradycardia was short lasting, and the cerebral vasodilatation persisted longest. It was not possible to predict the duration of action of PN on different target tissues by observing only one variable such as BP. Chloralose-urethane-anesthetized open-chest dogs appeared to be more sensitive to PN than cats. An i.v. dose of 3 mg/kg markedly increased coronary flow, lowered BP, increased CO, and tended to lower HR and to increase myocardial contractility. Myocardial O consumption was lowered. PN did not alter diastolic excitation threshold or any electrocardiog. intervals in closed-chest anesthetized dogs. Absence of myocardial depression, potent vasodilator activity, and long duration of action might render PN useful for the treatment of hypertension and angina pectoris.