UD-CG 115 ? a cardiotonic pyridazinone which elevates cyclic AMP and prolongs the action potential in guinea-pig papillary muscle

Honerjäger, P; Heiss, Alexander; Schäfer‐Korting, Monika; Schönsteiner, G.; Reiter, M.

doi:10.1007/bf00495953

Cited by 74 publications

(26 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…As a result, nearly a dozen agents have been developed such as amrinone (1, 2), AR-L 115 BS (sulmazole) (3, 4), MDL 17043 (5, 6), milrinone (7,8), MDL 19205 (piroximone) (9-11), OPC-8212 (12, 13), UD-CG 115 BS (14), 16), LY175326 (17), APP 201-533 (18,19), DPI 201-106 (20). Of these agents, except for DPI 201-106 (20), inhibition of cyclic AMP phosphodiesterase (PDE) and a resultant increase in intracellular cyclic AMP in myocardium have been proposed to be involved as a mechanism for the positive inotropic effect, although this may not be the sole mechanism.…”

Section: Abstract-cardiacmentioning

confidence: 99%

“…Of these agents, except for DPI 201-106 (20), inhibition of cyclic AMP phosphodiesterase (PDE) and a resultant increase in intracellular cyclic AMP in myocardium have been proposed to be involved as a mechanism for the positive inotropic effect, although this may not be the sole mechanism. 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).…”

Section: Abstract-cardiacmentioning

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%

See 4 more Smart Citations

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

Takahashi

Wada

Taira

1986

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

Section: Abstract-cardiacmentioning

confidence: 99%

See 3 more Smart Citations

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

Takahashi

Wada

Taira

1986

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

Pimobendan Increases Calcium Sensitivity of Skinned Human Papillary Muscle Fibers

Scheld¹,

Fritsche²,

Schlepper³

et al. 1989

The Journal of Clinical Pharma

View full text Add to dashboard Cite

The calcium sensitizing effects of the cardiotonic agent pimobendan on force production were investigated on chemically skinned human papillary muscle fibres. The papillary muscles were obtained from patients undergoing mitral valve replacement operations. Tension was produced by different free calcium concentrations and 100 mumol/l of pimobendan shifted the pCa-tension relationship significantly to the left. The effects of pimobendan were concentration dependent (10-300 mumol/l) but additionally also correlated with the state of left ventricular performance of the patients. Skinned papillary muscle fibres obtained from patients with reduced ventricular performance were more sensitive to calcium as well as pimobendan compared with fibres from patients with normal left ventricular performance. No differences in response to pimobendan were observed between fibres from NYHA II and NYHA III heart failure patients.

show abstract

Pyridazines. XV. Synthesis of 6‐aryl‐5‐amino‐3(2H)‐pyridazinones as potential platelet aggregation inhibitors

Estévez

Raviña

Sotelo

1998

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

show abstract

UD-CG 115 ? a cardiotonic pyridazinone which elevates cyclic AMP and prolongs the action potential in guinea-pig papillary muscle

Cited by 74 publications

References 23 publications

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

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

Pimobendan Increases Calcium Sensitivity of Skinned Human Papillary Muscle Fibers

Pyridazines. XV. Synthesis of 6‐aryl‐5‐amino‐3(2H)‐pyridazinones as potential platelet aggregation inhibitors

Contact Info

Product

Resources

About