Drugs online research references
Fed Proc. 1984 Apr;43(5):1333-5.
Initial evaluation of the non-sulfhydryl-containing converting enzyme inhibitor MK-521 in hypertensive humans.
Rotmensch HH, Vincent M, Vlasses PH, Swanson BN, Irvin JD, Hichens M, Harris KE, Ferguson RK.
MK-521 is a new orally active, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Single doses of 2.5, 5.0, 10.0, and 20.0 mg were administered to nine hypertensive patients alternating with placebo. All doses of MK-521 caused profound suppression of ACE activity for more than 24 h and decreased standing diastolic blood pressure for more than 12 h without changes in pulse rate. Although there was no further reduction in blood pressure with doses above 5.0 mg, the duration of action was prolonged for more than 24 h with the higher doses. Serum MK-521 concentrations increased with dosage, and ACE was inhibited maximally at concentrations above 10 ng/ml. In this initial study, MK-521 was well tolerated and proved to be a potent and long-acting antihypertensive agent.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6323225&dopt=Abstract
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Br J Clin Pharmacol. 1984 Mar;17(3):233-41.
Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man.
Hodsman GP, Zabludowski JR, Zoccali C, Fraser R, Morton JJ, Murray GD, Robertson JI.
The immediate and long-term effects of enalapril (MK421) and its lysine analogue (MK521) in once-daily dosage, were compared in a study of 12 normal subjects. Both compounds lowered blood pressure equally throughout 24 h without causing tachycardia. The biochemical changes with MK521 were more sustained than with MK421, but this did not affect the magnitude of blood pressure reduction. Twenty-four hours after the previous dose, with both active drugs, plasma renin concentration was significantly higher on day 8 than on day 1, though angiotensin I did not increase in proportion; this probably reflects a fall in renin-substrate with prolonged converting enzyme inhibition. There was an early natriuresis with each compound but this effect was no longer apparent after 8 days of continuous therapy. Both MK421 and MK521 were well tolerated with no serious side effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6324833&dopt=Abstract
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J Pharmacol Exp Ther. 1995 Nov;275(2):920-5.
Toxicodynamic analysis of cough and inflammatory reactions by angiotensin-converting enzyme inhibitors in guinea pig.
Ito K, Ito K, Sawada Y, Kamei J, Misawa M, Iga T.
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Angiotensin-converting enzyme (ACE) inhibitors are one of the first drugs of choice for the treatment of hypertension. However, there have been many reports of persistent chronic dry cough and inflammatory skin reactions (rash and/or angioedema, etc.) induced by ACE inhibitors. In this study, in order to evaluate the cough and inflammatory reaction, we measured the number of citric acid-induced coughs and the intradermal inflammation with ovalbumin in guinea pigs consecutively treated with ACE inhibitors (lisinopril, enalaprilat and imidapril) for 3 days. The number of citric acid-induced coughs and the inflammatory responses were significantly enhanced by treatment with lisinopril and enalaprilat, whereas imidapril produced no change in either response. These results correspond to the frequency of adverse effects in clinical practice, which suggests that imidapril has the least ability to induce the inflammatory skin response and cough. Furthermore, the enhancement produced by the ACE inhibitors in the number of coughs and the inflammatory responses were significantly reduced by pretreatment with indomethacin (prostaglandin synthesis inhibitor). This finding suggests that PGs at least participate in the mechanism for ACE inhibitor-induced cough and inflammatory skin response.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7473183&dopt=Abstract
word match zestril online literature
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