β-Adrenoceptor Blocking Activity of Diprafenone in Anesthetized Dogs

Greenberg, S; Cantor, Elinor H.; Paul, Jeff

doi:10.1097/00005344-198909000-00014

Cited by 17 publications

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“…On the day of the experiment the dogs were anesthetized with pentobarbital sodium (35 mgikg i.v . ) and maintained under surgical anesthesia with supplemental injections of pentobarbital sodium (1-3 mg/kg/hr), as required [Greenberg and Touhey, The animals were prepared for recording of hemodynamic parameters as described previously in detail [Greenberg et al, 1989;Greenberg and Touhey 199Oa-cl. Needles (23 gauge) were inserted into the left atrium and pulmonary artery for measurement of left atrial (LAP) and pulmonary arterial pressures (PAP), respectively.…”

Section: Materials and Methods Experimental Proceduresmentioning

confidence: 99%

Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK‐3197, a selective positive inotropic agent, in dogs with propranolol‐induced heart failure

Greenberg

Touhey

Hom

1991

Drug Development Research

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Greenberg, S., 6. Touhey, and G. Horn: Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK-3197, a selective positive inotropic agent, in dogs with propranolol-induced heart failure. Drug Dev. Res. 22:37-50, 1991. We examined the interaction between ouabain and CK-3197, a new selective positive inotrope, on the hemodynamic and myocardial energetic parameters of anesthetized dogs with propranolol-induced heart failure (PIHF). Mongrel dogs (13-18 kg) of either sex were anesthetized with pentobarbital sodium (35 mg/kg, i.v.) and instrumented for routine hemodynamic measurements using an open-chest, artificially ventilated preparation. PIHF was produced by decreasing left ventricular (LV) dP/dT max by 50% from control values with an initial infusion of 0.5 mg/kg of propranolol followed by continuous infusion of 0.02 to 0.08 mg/kg of propranolol to maintain PIHF. This was followed by infusion of saline (2 ml, i.v., n = 8/group) or ouabain (25 Fg/kg, i.v., n = Wgroup). Thirty minutes later one-half of the

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Section: Materials and Methods Experimental Proceduresmentioning

confidence: 99%

Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK‐3197, a selective positive inotropic agent, in dogs with propranolol‐induced heart failure

Greenberg

Touhey

Hom

1991

Drug Development Research

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“…Approximate plasma levels of diprafenone and propafenone in patients with the drugs at therapeutic doses were reported to be 0.1-2.0 g ml-' (Trenk et al, 1989;Kunze et al, 1989) and 0.5-3.0 tg ml1' (Siddoway et al, 1984;Greenberg et al, 1989) respectively. These ranges correspond roughly to 3 x 10-7 M-5 x o0-6 M diprafenone and 1-8 x 10-6 M propafenone.…”

Section: Discussionmentioning

confidence: 99%

“…Diprafenone was also shown to have P-adrenoceptor blocking activity, which was several times higher than propafenone (Greenberg et al, 1989;Groschner et al, 1991). These findings suggest that diprafenone, like propafenone, possesses Class-I as well as Class-II antiarrhythmic actions (Vaughan Williams, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…In vitro experiments in guinea-pig ventricular muscles have shown that diprafenone reduces the maximum upstroke velocity ( of the action potential without affecting the resting membrane potential, and that the Jma inhibition is enhanced in a frequency-dependent manner (Kohlhardt & Seifert, 1983;Kohlhardt & Fichtner 1988a). Diprafenone was also shown to have P-adrenoceptor blocking activity, which was several times higher than propafenone (Greenberg et al, 1989;Groschner et al, 1991). These findings suggest that diprafenone, like propafenone, possesses Class-I as well as Class-II antiarrhythmic actions (Vaughan Williams, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea‐pig ventricular cells

Kodama

Suzuki

Honjo

et al. 1992

British J Pharmacology

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“…Twenty-six mongrel dogs of either sex (10-18 kg body weight, five dogs per treatment group) were anesthetized with pentobarbital sodium (35 mg/kg, i.v. ), artificially ventilated with room air, and instrumented for measurement of blood pressure, myocardial dp/dt, and heart rate (HR) as described previously in detail [Greenberg and Touhey, 1990b,c;Greenberg et al, 1989a. After the animals equilibrated for 30 min, CK-2130, milrinone, enoximone, piroximone, imazodan, or ouabain was administered as intravenous infusions of increasing doses of a single test compound over a 5-min period with a subsequent 15-min observation period between each dose of compound.…”

Section: Materials and Methods In Vivo Studiesmentioning

confidence: 99%

General pharmacology of CK‐2130: A new selective positive inotrope

Greenberg

Paul

Luisi³

1990

Drug Development Research

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CK-2130 is a new imidazolone developed to treat congestive heart failure. We compared CK-2130 to four inodilators and ouabain in several pharmacologic models. Intravenous (i.v.) administration of CK-2130 to pentobarbital-anesthetized dogs (0.03 to 1 mg/kg) relatively selectively increased myocardial dP/dT when compared to the dual positive inotropic and vasodilator activity of milrinone, enoximone, imazodan, and piroximone. Milrinone and piroximone (600 mg/kg, P.o., and 30-300 mg/kg, i.p.) were central nervous system depressants in mice. CK-2130 (100 mg/kg, i.v. and 600 mg/kg, i.p. and p.0.) was not depressant. Gastric acid secretion in the guinea pig was not affected by CK-2130 (1 mg/kg, i.v.) and was inhibited by milrinone (1 mg/kg, i.v.) and enhanced by enoximone (1 mg/kg, i.v.). CK-2130 and milrinone (0.03-1 mg/kg, i.v.) did not affect rabbit sciatic nerve-gastrocnemius muscle function. CK-2130, piroximone, imazodan, and milrinone (100 pM) did not affect sympathetic neurotransmission, postsynaptic receptors, or guinea-pig nonvascular smooth muscles but relaxed canine arteries and veins. Ouabain (1-100 KM) initially facilitated, then inhibited, sympathetic neurotransmission, contracted vascular and non-vascular smooth muscles, enhanced the vas deferens contraction to norepinephrine, and inhibited uterine contractions to bradykinin (10 ELM). CK-2130, milrinone, piroximone, and imazodan (0.1 to 100 p,M) inhibited human platelet aggregation produced by adenosine diphosphate and sodium arachidonate. Thus, CK-2130, a relatively selective positive inotrope, should be devoid of adverse central nervous system; neural, smooth, and skeletal muscle; and gastrointestinal side effects associated with digitalis and enoximone therapy.

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β-Adrenoceptor Blocking Activity of Diprafenone in Anesthetized Dogs

Cited by 17 publications

References 0 publications

Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK‐3197, a selective positive inotropic agent, in dogs with propranolol‐induced heart failure

Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK‐3197, a selective positive inotropic agent, in dogs with propranolol‐induced heart failure

Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea‐pig ventricular cells

General pharmacology of CK‐2130: A new selective positive inotrope

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