Antihypertensive effects of the neutral endopeptidase inhibitor SCH 42495 in essential hypertension.
The antihypertensive effects and safety of a novel neutral endopeptidase inhibitor, SCH 42495, were investigated in hypertensive patients. A multicenter, open clinical trial was conducted in 27 patients with essential hypertension, WHO Stage I or II. Mean age was 64 +/- 1 years. After 2 to 4 weeks of a placebo run-in, 50 mg twice daily, was started, with the dose increased to 100 mg twice daily, and 200 mg twice daily, every 2 weeks, if necessary, to achieve a predetermined response. Blood pressure and pulse rate were monitored every 2 weeks. Blood chemistry, plasma atrial natriuretic peptide (ANP), and plasma cGMP levels were determined before and after the 8-week treatment period. Blood pressure was significantly reduced, from 171 +/- 1/100 +/- 1 mm Hg to 146 +/- 3/84 +/- 2 mmHg (P < .001) at the end of the 8-week treatment period. No change in pulse rate was noted. Efficacy rate was evaluated in 25 patients treated for 4 weeks or more. Efficacy rate was 44% with 50 mg twice daily, 60% with 100 mg twice daily, and 80% with 200 mg twice daily. Adverse reactions such as headaches and palpitation were observed in six patients (22.2%), with treatment discontinued in five. Significant correlation was observed between increment in plasma ANP levels and blood pressure reductions (r = -0.53, P < .05). Increase in plasma cGMP was positively correlated with increments in plasma hANP (r = 0.80, P < .001). SCH 42495 has potent antihypertensive effect associated with an enhancement of endogenous hANP and may be clinically useful as a new class of antihypertensive drug.
Department of Geriatric Medicine, Osaka University Medical School, Japan.
T
T
Ogihara
H
H
Rakugi
K
K
Masuo
H
H
Yu
M
M
Nagano
H
H
Mikami
D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*
D000959:Antihypertensive Agents; C069018:SCH 42495; D009320:Atrial Natriuretic Factor; D008715:Methionine; D015260:Neprilysin; D006152:Cyclic GMP