Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent

• Published in: European journal of clinical pharmacology Vol. 20; no. 6; p. 399
• Main Authors: Kawasaki, T, Uezono, K, Abe, I, Nakamuta, S, Ueno, M, Kawazoe, N, Omae, T
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1981
• Subjects: Adrenergic alpha-Antagonists - pharmacology; Adult; Aged; Aldosterone - blood; Blood Pressure - drug effects; Chemical Phenomena; Chemistry; Dopamine beta-Hydroxylase - blood; Epinephrine - blood; Female; Humans; Male; Middle Aged; Norepinephrine - blood; Posture; Pulse - drug effects; Quinazolines - pharmacology; Renin - blood
• ISSN: 0031-6970
• DOI: 10.1007/BF00542090

To determine whether E-643, a new alpha-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37--73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-beta-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172 +/- 31/100 +/- 12 leads to 151 +/- 28/89 +/- 14 mmHg), sitting (158 +/- 22/101 +/- 11 leads to 138 +/- 28/89 +/- 15 mmHg) and standing (153 +/- 32/103 +/- 21 leads to 129 +/- 31/89 +/- 20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67 +/- 10 leads to 69 +/- 10 beats/min), but was increased in the sitting (68 +/- 10 leads to 73 +/- 9 beats/min) and standing (73 +/- 10 leads to 81 +/- 11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-beta-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-beta-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.