Enalapril inhibitors

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Folic acid deficiency Hyperthermia Phenylketonuria Rheumatic disease Virilizing tumors Drugs and chemicals Androgenic chemicals Angiotensin-converting enzyme inhibitors Captopril, enalapril Antibiotics... 

More than 15 ACE inhibitors are presently available. They belong to three different chemical classes sul-fhydryl compounds such as captopril, carboxyl compounds such as enalapril, and phopshorus compounds... 

Angiotensm-converting enzyme (ACE) inhibitors— for example, captopril (Capoten), enalapril (Vasotec), and lismopril (Prinivil)... 

The nitrate-hydralazine combination was first shown to improve survival compared to placebo.27 Subsequently, the combination of isosorbide dinitrate 40 mg and hydralazine 75 mg, both given four times daily, was compared to the ACE inhibitor enalapril.28 Enalapril produced a 28% greater decrease in mortality. Therefore, the combination is considered a third-line vasodilatory option for patients truly intolerant of ACE inhibitors and ARBs. 

Enalaprilat and SQ27,519 are angiotensin-converting enzyme (ACE) inhibitors with poor oral absorption. Enalapril and fosinopril are dipeptide and amino acid derivatives of enalaprilat and SQ27,519, respectively [51] (Fig. 10). Both prodrugs are converted via deesterification to the active drug by hepatic biotransformation. In situ rat perfusion of enalapril indicated a nonpassive absorption mechanism via the small peptide carrier-mediated transport system. In contrast to the active parent, enalapril renders enalaprilat more peptide-like, with higher apparent affinity for the peptide carrier. The absorption of fosinopril was predominantly passive. Carrier-mediated transport was not demonstrated, but neither was its existence ruled out. 

DI Friedman, GL Amidon. Passive and carrier-mediated intestinal absorption components of two angiotensin converting enzyme (ACE) inhibitor prodrugs in rats Enalapril and fosinopril. Pharm Res 6(12) 1043-1047, 1989. 

Captopril 678 and enalapril 679 are potent angiotensin converting enzyme (ACE) inhibitors used as antihypertensives. Molecular manipulation based on the enzyme model led to the discovery of some perspective bicyclic structures, for example, cilazapril 680 and compound 681, highly active antihypertensives in vivo. Compound 681 belongs to the most potent conformationally restricted ACE inhibitors and is often used as a model for molecular modeling studies <1996JA8231>. 

Swaan, P. W., Stenhouwer, M. C., Tukker, J., Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors enalapril, enalaprilat, and lisinopril, Biochim. Biophys. Acta 1995, 3236, 31-38. 

Angiotensinogen converting ACE-inhibitors (enalapril, Variation of ACE efficacy in the treatment of Susceptibility to essential hyperten-... 

All 10 ACE inhibitors available in the United States can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril (but not enalapril or lisinopril) is reduced by 30% to 40% when given with food. 

Some optically active compounds have been studied [54], The benzazepinone diacid (CGS 12831, 27) was found to have the best in vitro inhibitor potency in a series of lactam compounds, but it showed only marginal biological activity following oral administration, presumably because of poor absorption. The corresponding monoethyl ester (CGS 14824A, 28) was much more potent in vivo [54, 56]. This compound (28) was found to produce dose-dependent antihypertensive effects in conscious normotensive and spontaneous hypertensive rats, generally similar to those produced by enalapril. Evaluation of (28) in healthy volunteers [57, 58] shows that it is an effective,... 

Minsker, D., Bagdon, W., MacDonald, J., Robertson, R. and Bokelman, D. (1990). Matemo-toxicity and fetotoxicity of an angiotensin-converting enzyme inhibitor, enalapril, in rabbits. Fund. Appl. Toxicol. 14 461-479. 

Peptidyl-dipeptidase A (angiotensin-I converting enzyme, ACE, EC 3.4.15.1) plays a pivotal role in the control of blood pressure [80]. It has been established that its active site contains an essential Zn-atom that functions like that of carboxypeptidase A [2], ACE is inhibited by peptides having a proline or aromatic amino acid at the C-terminal position. These observations as well as the similarities with the active site of carboxypeptidase A have allowed a rational design of effective inhibitors of ACE (e.g., captopril (3.4) and enalapril (3.5)) used in the treatment of hypertension [81]. 

P. W. Swaan, M. C. Stehouwer, J. J. Tukker, Molecular Mechanism for the Relative Binding Affinity to the Intestinal Peptide Carrier. Comparison of Three ACE-Inhibitors Enalapril, Enalaprilat and Lisinopril , Biochim. Biophys. Acta 1995, 1236, 31-38. 

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