Studies on the Mechanism of the Positive Inotropic Effect of Piroximone in Cat Papillary Muscle

Hc, Cheng; Kariya, Takashi; Em, Gleason; Rc, Dage

doi:10.1097/00005344-198507000-00020

Cited by 8 publications

(3 citation statements)

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“…The decrease in AV conduction time produced by a 10-fold increase in dose was about 12% for both IBMX and theophylline. The doses (AVCTED 10%) which produced a 10% decrease in AV conduction time were 21 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] nmol for I BMX and 1.1 [0.7-1.6] ;imol for theophylline.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, PDE inhibitory activity in crude enzyme or purified enzyme (isozyme III) preparations has been demonstrated for amrinone (21,22), sulmazole (23-25), MDL 17043 (6, 25), milrinone (7), piroximone (11), OPC-8212 (13), UD-CG 115 BS (14), and APP 201-533 (18). Elevation of intra cellular cyclic AMP in myocardium at drug concentrations producing a positive inotropic effect has been demonstrated for amrinone (21,22), sulmazole (25), MDL 17043 (25), milrinone (7), piroximone (26), OPC-8212 (13,27), UD-CG 115 BS (14), and APP 201-533 (19). Thus, it was of interest to know whether and how these agents are different in cardiovascular profile from classical PDE inhibitors.…”

Section: Abstract-cardiacmentioning

confidence: 99%

“…3-Isobutyl-1-methylxanthine (IBMX) is known to be more specific than theophylline as a PDE inhibitor (28) and has been used as a reference drug in studies dealing with the relation between changes in intracellular cyclic AMP and positive inotropy (14,21,22,26). Nevertheless, little infor mation is available about its detailed cardiac vs. coronary vasodilator actions.…”

Section: Abstract-cardiacmentioning

confidence: 99%

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Cardiac versus Coronary Vasodilator Actions of Isobutylmethylxanthine in Dogs: Comparison with Theophylline

Takahashi

Wada

Taira

1986

Japanese Journal of Pharmacology

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Abstract-Cardiacand coronary vasodilator effects of isobutylmethylxanthine (I BMX) and theophylline were compared in isolated, blood-perfused papillary muscle, sino-atrial (SA) node and atrioventricular (AV) node preparations of dogs. I BMX (1 nmol-1 /mol) and theophylline (30 nmol-10 /tmol) were injected intra arterially.In paced papillary muscle preparations, both agents increased the force of contraction.In spontaneously beating papillary muscle preparations, both agents increased the rate of ventricular automaticity.In SA node preparations, both agents increased sinus rate. In AV node preparations, both agents decreased AV conduction time only when they were injected into the artery supplying the AV node.In all preparations, both agents increased coronary blood flow. However, both agents were not homogeneously effective on these cardiovascular variables, but showed selectivity in the following order: Ventricular muscle contraction coronary blood flow>SA nodal automaticity -*.AV nodal conduction>ventricular automaticity.These results indicate that IBMX and theophylline have almost an identical profile in their cardiac and coronary vasodilator effects.The two agents were different in that IBMX was 40-50 times as potent as theophylline in producing these effects.Thus, both agents appeared to express their cardiovascular profiles mainly through inhibition of cyclic AMP phosphodiesterase, although theophylline has been claimed to have additional actions.Recently, an intensive search has been carried out to find new non-sympathomimetic and non-glycoside positive inotropic agents (simply called novel positive inotropic agents hereafter) which can replace digitalis. As a result, nearly a dozen agents have been developed such as amrinone (1, 2), AR-L 115

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Section: Discussionmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

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Cardiac versus Coronary Vasodilator Actions of Isobutylmethylxanthine in Dogs: Comparison with Theophylline

Takahashi

Wada

Taira

1986

Japanese Journal of Pharmacology

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P

Bruchhausen

Ebel

Hackenthal³

et al. 1999

Hagers Handbuch Der Pharmazeutischen Praxis

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Actions of the phosphodiesterase inhibitor zardaverine on guinea-pig ventricular muscle

Galvan

Schudt

1990

Naunyn-Schmiedeberg's Arch Pharmacol

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The positive inotropic action of the phosphodiesterase inhibitor zardaverine was investigated in guinea-pig heart muscle. In right papillary muscles, 1-30 microM zardaverine reversibly increased the force of contraction in a concentration-dependent manner. This effect was accompanied by a shortening of contraction and relaxation times. Resting membrane potential was unchanged, whereas action potential amplitude was significantly increased and duration was reduced. In papillary muscles partially depolarised with 22 mM K+, zardaverine (10 and 30 microM) restored slow action potentials, which were not influenced by cimetidine, propranolol or prazosin but were blocked by the calcium channel blocker (+)-nitrendipine or the muscarinic agonist carbachol. cAMP-specific phosphodiesterase III, isolated from guinea-pig ventricular muscle was inhibited by zardaverine as was cAMP-specific phosphodiesterase IV, isolated from dog trachea (IC50s: 0.5 and 0.8 microM, respectively). The results suggest that the observed positive inotropic and electrophysiological effects result from an inhibition of cellular phosphodiesterase.

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Studies on the Mechanism of the Positive Inotropic Effect of Piroximone in Cat Papillary Muscle

Cited by 8 publications

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Cardiac versus Coronary Vasodilator Actions of Isobutylmethylxanthine in Dogs: Comparison with Theophylline

Cardiac versus Coronary Vasodilator Actions of Isobutylmethylxanthine in Dogs: Comparison with Theophylline

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Actions of the phosphodiesterase inhibitor zardaverine on guinea-pig ventricular muscle

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