Summary
The time course of the blood pressure lowering effect and the dose-response relationship of the new angiotensin converting enzyme inhibitor ramipril (HOE 498) were studied in 8 patients with essential hypertension. As compared with placebo, a single oral dose of 2.5 mg ramipril lowered systolic and diastolic blood pressure. The antihypertensive action of single oral doses of 5, 7.5 and 10 mg ramipril was more pronounced. No change in heart rate occurred. Angiotensin converting enzyme activity was suppressed after all doses of ramipril studied. Plasma renin activity increased after 2.5 mg and 5 mg ramipril. Plasma aldosterone was not affected by 2.5 mg, but it fell after 5 mg ramipril. Thus, ramipril produced prolonged inhibition (more than 12 hours) of angiotensin converting enzyme activity and lowered blood pressure in patients with essential hypertension.
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Becker RHA, Schölkens BA, Metzger H, Schulze KJ (1984) Pharmacological properties of the new orally active converting enzyme inhibitor HOE 498. Arzneimittelforsch 34: 1411–1416
Becker RHA, Schölkens BA, Unger Th, Linz W (1983) HOE 498: An orally active nonsulphydryl ACE-inhibitor. Naunyn Schmiedebergs Arch Pharmacol 324: R42
Böhm R, van Baak M, Mooy J, Rahn KH (1985) Studies of the antihypertensive effect of the angiotensin-converting enzyme inhibitor HOE 498 in man. Naunyn Schmiedebergs Arch Pharmal 330 [Suppl]: R47
Brunner HR, Gavras H, Waeber B, Kersha GR, Turini GA, Kukovich RA, McKinstry DN, Gavras J (1979) Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Int Med 90: 19–23
Brunner DB, Desponds G, Biollaz J, Keller J, Ferber F, Gavras H, Brunner HR, Schelling JL (1981) Effect of a new angiotensin converting enzyme inhibitor MK 421 and its lysine analogue on the components of the renin system in healthy subjects. Br J Clin Pharmacol 11: 461
Bussien JP, Nussberger J, Porchet M, Waeber B, Brunner HR, Perisic M, Tansey MJ, Bomm M, Hajdu P (1985) The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers. Naunyn Schmiedebergs Arch Pharmacol 329: 63–69
Davies RO, Jevin JD, Kramsch DK, Walter JF, Moncloa F (1984) Enalapril worldwide experience. Am J Med 77 [Suppl]: 23–35
Felder K, Witte PU (1984) Effects of the new oral angiotensin converting enzyme inhibitor 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (HOE 498) in essential hypertension. Arzneimittelforsch 34: 1452–1454
Ferguson RK, Vlasses PH, Swanson BN, Mojaverian P, Hichens M, Irvin JD, Huber PB (1982) Effects of enalapril, a new converting enzyme inhibitor in hypertension. Clin Pharmacol Ther 32: 48–53
Frohlich ED, Cooper RA, Lewis EJ (1984) Review of the overall experience of captopril in hypertension. Arch Intern Med 144: 1441–1444
Heel RC, Brogden RN, Speight TM, Avery GS (1980) Captopril: A preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 20: 409–452
Henquet JW, Kho T, Schols M, Thijssen H, Rahn KH (1981) The sympathetic nervous system and the renin-angiotensin system in borderline hypertension. Clin Sci 60: 25–31
Jackson B, McGrath BP, Johnson CJ (1982) Correlation between angiotensin converting enzyme inhibition and the acute hypotensive response to MK 421 in essential hypertension. Clin Exp Pharmacol Physiol [Suppl 7]: 99–104
Johnston CI, Jackson B, McGrath B, Matthews G, Arnolda L (1983) Relationship of antihypertensive effect of enalapril to serum MK-422 levels and angiotensin converting enzyme inhibition. J Hypertension 1 [suppl 1]: 71–75
Johnston CI, Arnolda L, Hiwatari M (1984) Angiotensin-converting enzyme inhibitors in the treatment of hypertension. Drugs 27: 271–277
Lijnen P, Amery A, Fagard R, Corvol P (1978) Direct radioimmunoassay of plasma aldosterone in normal subjects. Clin Chim Acta 84: 305–314
Manhem PJO, Ball SG, Morton JJ, Murray GD, Leckie BJ, Fraser R, Robertson JI (1985) A dose-response study of HOE 498, a new non-sulphydryl converting enzyme inhibitor, on blood pressure, pulse rate and the renin-angiotensin-aldosterone system in normal man. Br J Clin Pharmacol 20: 27–35
Riley LJ, Vlasses PH, Ferguson RK (1985) Clinical pharmacology and therapeutic applications of the new oral converting enzyme inhibitor enalapril. Am Heart J 109: 1085–1089
Ryan JW, Chung A, Ammons C, Carlton ML (1977) A simple radio-assay for angiotensin converting enzyme. Biochem J 167: 501–504
Schölkens BA, Becker RHA, Kaiser J (1984) Cardiovascular and antihypertensive activities of the novel non-sulphydryl converting enzyme inhibitor HOE 498. Arzneimittelforsch 34: 1417–1425
Shoback DM, Williams GH, Swartz SL, Davies RO, Hollenberg NK (1983) Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK 421) in normal subjects. J Cardiovasc Pharmacol 5: 1010–1018
Unger T, Ganten D, Lang RE, Schölkens BA (1984) Is tissue converting enzyme inhibition a determinant of the antihypertensive efficacy of converting enzyme inhibitors? Studies with the two different compounds, HOE 498 and MK 421, in spontaneously hypertensive rats. J Cardiovasc Pharmacol 6: 872–880
Waeber B, Brunner HR, Brunner DB, Curtet AL, Turini GA, Gavras H (1980) Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. Hypertension 2: 236–242
Witte PU, Irmisch R, Hajdu P, Metzger H (1984a) Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects. Eur J Clin Pharmacol 27: 577–581
Witte PU, Metzger H, Eckert HG, Irmisch R (1984b) Tolerance and pharmacodynamics of the angiotensin-converting enzyme inhibitor 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid HOE 498 in healthy volunteers. Arzneimittelforsch 34: 1448–1451
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Dedicated to Professor Dr. P. Schölmerich on the occasion of his 70th birthday
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Böhm, R.O.B., van Baak, M.A. & Rahn, K.H. Studies on the antihypertensive effect of single doses of the angiotensin converting enzyme inhibitor ramipril (HOE 498) in man. Eur J Clin Pharmacol 30, 541–547 (1986). https://doi.org/10.1007/BF00542412
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DOI: https://doi.org/10.1007/BF00542412