Detail of "95399-71-6"

Reference

Vasopeptidase inhibition in a canine model of exercise-induced left ventricular dysfunction

Vasopeptidase inhibition in a canine model of exercise-induced left ventricular dysfunction. Holzgrefe, Henry H.; Arthur, Susan R.; Powell, James R. (Bristol-Myers Squibb Pharmaceutical Research Institute, Pennington, NJ, USA). Clinical and Experimental Pharmacology and Physiology, 29(8), 696-703 (English) 2002 Blackwell Publishing Asia Pty Ltd. CODEN: CEXPB9. ISSN: 0305-1870. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The present study compared the acute efficacies of vasopeptidase inhibition with omapatrilat, nitroglycerin and angiotensin-converting enzyme (ACE) inhibition in exercise-induced myocardial dysfunction. Omapatrilat, a vasopeptidase inhibitor, inhibits both neutral endopeptidase and ACE. Whereas vasopeptidase inhibitors have demonstrated clin. efficacy in hypertension and heart failure, their effects in myocardial ischemia remain unclear. Omapatrilat (0.3 mg/kg) was compared with vehicle (saline), an ACE inhibitor (fosinoprilat; 0.44 mg/kg) and nitroglycerin (8.0 mg/kg per min), in an established canine model of exercise-induced myocardial dysfunction induced by progressive closure of an ameroid constrictor placed about the proximal circumflex coronary artery. Maximal treadmill exercise tests, terminated when heart rate failed to increase with increasing workload or failure to continue exercise, were performed in chronically instrumented dogs. During exercise, omapatrilat and nitroglycerin similarly increased ischemic wall thickening (P ￡ 0.0001, ANOVA, 12 d.f.), whereas fosinoprilat and vehicle were without effect. Ischemic zone ST changes were decreased with nitroglycerin (P = 0.0006, ANOVA, 12 d.f.) and tended to decrease with omapatrilat (P = 0.07, ANOVA, 12 d.f.). Peak exercise capacity was increased with nitroglycerin (9.7±1.1 vs. 11.2±1.0 kcal, control vs.Several substances with their cas registry numbers 95399-71-6 and 9015-82-1 may be metioned in this study. 4 h, resp.; n = 6) and omapatrilat (9.7±0.8 vs. 11.4±0.6 kcal, control vs. 4 h, resp.; n = 6) and was unchanged with ACE inhibition (9.0±1.2 vs. 9.5±1.1 kcal, control vs. 4 h, resp.; n = 7). Omapatrilat differentially increased double product during exercise (P = 0.001, ANOVA, 12 d.f.) compared with other treatments. During exercise-induced myocardial dysfunction, acute ACE inhibition did not attenuate ischemic changes and failed to improve exercise capacity. Increased exercise capacity with omapatrilat was accompanied by a differential increase in double product, consistent with increased oxygen supply and demand. Improvements in ischemic function were comparable between omapatrilat and nitroglycerin, suggesting that omapatrilat may represent a novel therapy in demand-induced ischemia. .

The future of angiotensin-converting enzyme inhibitors

The future of angiotensin-converting enzyme inhibitors. Mackaness, G. B. (Squibb Inst. Med. Res., Princeton, NJ 08540, USA). J. Cardiovasc. Pharmacol., 7(Suppl. 1), 30-4 (English) 1985. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review with 8 refs. on the historical development and the classification of angiotensin-converting enzyme inhibitors by chem. structure and the considerations involved in developing new and improved drugs of this pharmacol. class. Because renal disease is a common cause of hypertension and the 2 conditions frequently coexist, in some patients, agents that are eliminated by both renal and hepatobiliary routes may be more desirable than those eliminated almost exclusively by the kidneys. This and other shortcomings have led to the development of 2 new angiotensin-converting enzyme inhibitors, zofenopril [81872-10-8] and fosfenopril [95399-71-6], both of which are in the early phase of clin. investigation.