High impact information on SK&F 94120

• The first, PDE III, had apparent Km values of 0.3 microM (cAMP) and 8 microM (cGMP) and was inhibited by cGMP (IC50 = 0.1 microM), SK&F 94120 (Ki = 7.8 microM), and SK&F 94836 (Ki = 0.4 microM) [1].
• The drug SK&F 94120 selectively and competitively inhibited PDE III with a Ki value of 0.8 microM (human), showing simple hyperbolic inhibition kinetics [2].
• 1 The anti-spasmogenic potential of SK&F 94120 (PDE3-selective), rolipram (PDE4-selective), zaprinast (PDE5-selective), zardaverine (dual PDE3/4 inhibitor) and theophylline (non-selective) was evaluated in guinea-pig trachealis [3].
• 8. In intact macrophages, Ro 20-1724 and RS-rolipram potentiated isoprenaline-induced cyclic AMP accumulation under conditions where a PDE3 inhibitor, SK&F 94120, was essentially inactive [4].
• Cyclic AMP-elevating agents used were a beta-adrenoceptor agonist (isoprenaline), a phosphodiesterase 3 (PDE3) inhibitor (SK&F 94120) and a PDE4 inhibitor (rolipram) [5].

Biological context of SK&F 94120

• However, SK&F 94120 selective for cyclic AMP-PDE (PDE III), primarily responsible for the metabolism of adenosine 3':5'-cyclic monophosphate (cyclic AMP), resulted in vasodilatation only at very high concentrations [6].
• In both the cytosolic and the membrane preparations, the hydrolysis of cAMP was inhibited by 100 microM of either the PDE III inhibitor SK&F 94120 (27% and 31% respectively) or the PDE IV inhibitor rolipram (14% and 23% respectively) [7].
• Haemodynamic studies in anaesthetized cats indicated that, as a consequence of the positive inotropic and vasodilator actions, SK&F 94120 causes significant increases in cardiac output and stroke volume [8].

Anatomical context of SK&F 94120

• SK&F 94120 was found selectively to inhibit the "low Km" PDE III activity with an IC50 of 10.8 microM, which is consistent with the effects of this compound on cardiac ventricle PDE activities [9].
• The inotropic effects of the selective phosphodiesterase (PDE) III inhibitors, SK&F 94120 and SK&F94836, and the non-selective PDE inhibitor, 3-isobutyl-l-methylxanthine (IBMX), alone and when combined synergistically with isoprenaline, were studied in control and beta-adrenoceptor-desensitized ventricular myocytes [10].
• 1. The effect on cyclic nucleotide contents of selective inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoforms III and IV (respectively SK&F 94120 and rolipram) and their interactions with endothelium and NO have been studied in rat aorta in the presence of indomethacin (10 microM) [11].
• The actions of SK&F 94120, a selective phosphodiesterase (PDE III) inhibitor, have been characterised on human ventricular myocardium obtained from heart failure patients [12].

Associations of SK&F 94120 with other chemical compounds

• In this study we have investigated the effects of SK&F 94120 on human platelet phosphodiesterase (PDE) activities separated by ion-exchange chromatography, and studied the effects of this agent on platelet responses caused by the agonists collagen, U44069 and ADP [9].
• AH-21-132 (IC50 greater than 10 microM), SK&F 94120 (IC50 greater than 10 microM) and zaprinast (IC50 greater than 10 microM) were without effect [13].

Gene context of SK&F 94120

• Similarly, neither SK&F 94120 (10 microM) nor rolipram (10 microM), selective inhibitors of PDE3 and PDE4 respectively, significantly affected the release of ACh in response to EFS [14].
• The analysis of SK&F 94120, a novel inotropic agent, and its four metabolites by isolation on C18 AASP cassettes followed by high-performance liquid chromatography [15].

Analytical, diagnostic and therapeutic context of SK&F 94120

• Analysis of 5-(4-acetamidophenyl)pyrazin-2(1H)-one (SK&F 94120) in plasma with an Analytichem automated sample processor liquid chromatography module [16].

References