Rousso P Buclin T Nussberger J Brunner-Ferber F Brunner HR Biollaz J 1998 MDL 100,240, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), was administered intravenously to two panels of four healthy males in a four-period, dose-increasing (0, 1.56, 6.25, and 25 mg, and 0, 3.13, 12.5, and 50 mg, respectively) double-blind, placebo-controlled study. Plasma ACE activity and blood-pressure response to exogenous angiotensin I and angiotensin II i.v. challenges and safety and tolerance were assessed over a 24-h period. MDL 100,240 induced a rapid, dose-related, and sustained inhibition of ACE (>70% over 24 h at doses > or =12.5 mg). The time integral of ACE inhibition was related to the dose but with near-maximal values already attained at doses > or =12.5 mg. Systolic and diastolic blood-pressure responses to exogenous angiotensin I challenges were inhibited in a dose-dependent fashion, whereas the effects of angiotensin II remained unaffected. Mean supine blood pressure decreased transiently (3 h) at doses > or =3.125 mg and < or =24 h with the 25- and 50-mg doses, but not significantly. MDL 100,240 was well tolerated. In healthy subjects, MDL 100,240 exerts a dose-dependent and long-lasting ACE-blocking activity, also expressed by the inhibition of the pressor responses to exogenous angiotensin I challenges. The baroreceptor reflex, assessed by the response to exogenous angiotensin II challenge, remains unaltered. https://sonar.ch/global/documents/189422 eng info:eu-repo/semantics/altIdentifier/doi/10.1097/00005344-199803000-00012 info:eu-repo/semantics/altIdentifier/pmid/9514186 Journal of cardiovascular pharmacology. - 1998 Adult Angiotensin I Angiotensin II Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Area Under Curve Benzazepines Blood Pressure Double-Blind Method Enzyme Inhibitors Humans Male Neprilysin Placebos Pyridines Reference Values Effects of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase on the vasopressor response to exogenous angiotensin I and angiotensin II challenges in healthy volunteers. http://purl.org/coar/resource_type/c_6501