Disease relevance of CI 930

• Acute hemodynamic and hormonal effects of CI-930, a new phosphodiesterase inhibitor, in severe congestive heart failure [1].
• Effects of CI-930 on hemostasis, thrombosis, and AA-induced hemodynamic reaction [2].

High impact information on CI 930

• The most selective PDE III inhibitor was CI-930 (10), the 5-methyl analogue of imazodan (CI-914, 1), with an IC50 of 0.6 microM [3].
• (Possible reasons for the potency of certain nonplanar compounds are discussed.) Cardiotonics like imazodan (1; CI-914) and 2 (CI-930) can readily achieve essentially planar geometries, as shown with X-ray crystallographic, IR, UV, NMR, and theoretical data [4].
• Twenty micromolar CI-930 and 20 microM rolipram used individually attenuated proliferation of HCASMC from some, but not all donors, as measured by flow cytometry [5].
• The results indicate that human T-lymphocytes contain both CI-930- and Ro 20-1724-inhibitable isozymes [6].
• Whereas CI-930 was approximately equipotent inhibiting PDE IIIc and relaxing rolipram-pretreated trachea, rolipram was substantially more potent (EC50 = 0.02 microM) in relaxing CI-930-pretreated trachea than in inhibiting CI-930-pretreated PDE III (PDE IIIRO, IC50 = 2.6 microM) [7].

Biological context of CI 930

• At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05) [8].
• Cardiac output (CO) was not affected by CI-930 [9].
• CI-930 at 3 mg/kg increased the heart rate (HR), maximal aortic flow acceleration (dF/dt), and peak aortic flow and decreased the stroke volume (SV) [9].
• We had expected that the vasodilatation induced by 3l, as efficient as reference PDE3 inhibitors, milrinone or CI-930, to be due to PDE3 inhibition [10].
• For inhibition of cAMP hydrolysis, IC50 values were: for cGMP = 0.6 microM and for OPC 3911, milrinone, CI 930, 0.1-2.0 microM [11].

Anatomical context of CI 930

• When various phosphodiesterase (PDE) inhibitors were tested for their effects on R59022-induced oocyte maturation, papaverine (a potent nonselective inhibitor of PDE) and CI-930 (a selective PDE III inhibitor) were observed to significantly inhibit the R59022-stimulated response [12].
• In addition, CI-930 protected rabbit from all the harmful hemodynamic responses to the occlusion of pulmonary microcirculation, which was induced by AA [2].
• In the concentration range of 0.5-500 mumols/L, CI-930 reduced the synthesis of TXB2 by either washed rat or rabbit platelets or rat pleural neutrophils [13].

Associations of CI 930 with other chemical compounds

• The selective PDE III inhibitors CI-930 and cilostamide used alone attenuated DNA synthesis with EC50 values (> 300 and 5.3 microM, respectively) that were much higher than published IC50 values (0.15-0.46 and 0.005-0.064 microM, respectively) for inhibition of PDE III [14].
• Rolipram and CI-930 exhibited biphasic concentration-response relationships for relaxation of carbachol-, histamine- and leukotriene D4-contracted trachea [7].
• Effects of CI-930, a novel phosphodiesterase III inhibitor, on platelet aggregation and arachidonic acid metabolism [13].
• 2. The best inhibitors of the hydrolysis of 1 microM cAMP were SQ 65.442 (IC50 c 10 microM), dipyridamol and CI 930. cGMP was not an inhibitor (IC50 greater than 1000 microM) [15].

Gene context of CI 930

• Hemodynamic, pharmacokinetic and clinical response to CI-930 in congestive heart failure due to ischemic or dilated cardiomyopathy [8].
• The cost of healthcare for the lenograstim group (excluding lenograstim acquisition costs) was 700 pounds higher per patient than that for the group not treated with lenograstim (95% CI -930 pounds to 2300 pounds) [16].
• IL-2 transcription was greatly inhibited by 1 microM CsA, whereas neither 10 microM rolipram nor 10 microM CI-930 had any effect on steady-state levels of IL-2 mRNA [17].

Analytical, diagnostic and therapeutic context of CI 930

• Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration [8].

References