Reference

b-Blocking and hemodynamic effects of ASL-8052

b-Blocking and hemodynamic effects of ASL-8052. Gorczynski, Richard J.; Murthy, V. Shrinivas; Hwang, Tsae Fung (Dep. Pharm. Res., Am. Crit. Care, McGaw Park, IL 60061, USA). J. Cardiovasc. Pharmacol., 6(6), 1048-59 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) ASL-8052 (esmolol)(I) [81161-17-3] produced dose-dependent redns. in heart rate, left ventricular dP/dt, right ventricular contractile force, and diastolic arterial blood pressure in anesthetized dogs with intact autonomic function. I was devoid of any hemodynamic effects in ganglion-blocked animals. Responses to isoproterenol [7683-59-2] (except for diastolic blood pressure) were blocked by I in qual. similar fashions in both groups of animals. The compd. reduced the rate-pressure product and decreased diastolic coronary blood flow. The reactive hyperemic response to a 10-s occlusion of the left circumflex coronary artery was not modified by I. Heart rate and contractile force dose-response curves to isoproterenol were equally shifted to the right in a dose-dependent, parallel fashion by const. infusion of I. During infusion of large doses in reserpinized dogs, the compd. decreased heart rate, contractility, and arterial blood pressure, but left ventricular end-diastolic pressure increased. No intrinsic sympathomimetic effect was obsd. Tachycardia induced by either stimulation of the right ansa subclavia or i.v. injection of isoproterenol was blocked to an equiv. degree by I. I produces hemodynamic effects that are characteristic of and explained by b-adrenergic receptor blockade. However, direct cardiac depression is obsd. at extremely high doses.

Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite

Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite. Sum, Check Y.; Yacobi, Avraham; Kartzinel, Ronald; Stampfli, Herman; Davis, Charles S.; Lai, Chii Ming (Res. Dev. Dep., Am. Crit. Care, McGaw Park, IL, USA). Clin. Pharmacol. Ther. (St. Louis), 34(4), 427-34 (English) 1983. CODEN: CLPTAT. ISSN: 0009-9236. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Esmolol [81161-17-3] was studied in 8 healthy subjects after continuous i.v. infusion of 400 mg/kg/min over 2 h. The concns. of esmolol and its major metabolite, 3-[4-(2-hydroxy-3-{isopropylamino}propoxy)phenyl]propionic acid [81148-15-4], in blood and urine were detd. by gas chromatog.-mass spectrometric assay and high-performance liq. chromatog. The distribution and elimination t1/2's of esmolol averaged 2.03 and 9.19 min. The apparent vol. of distribution of esmolol averaged 3.43 l/kg and was 4-times the vol. 81161-17-3 and 81148-15-4 are cas registry numbers of chemicals which are used as reagents here. of the central compartment. The total clearance of esmolol averaged 285 mL/min/kg, indicating that nonhepatic routes play a predominant role in its clearance. The t1/2's of formation and elimination of the metabolite averaged 2.82 min and 3.72 h. The ratio of the metabolite formation and elimination rate consts. of the parent drug (kf/k10) averaged 0.829, suggesting that 82.9% of esmolol was converted to the metabolite (which is consistent with the urinary recovery of 71% of the dose as unconjugated metabolite). The vol. of distribution and total clearance of the metabolite averaged 0.411 l/kg and 1.28 mL/min/kg. Esmolol was followed by a significant redn. of isoproterenol-induced increase in heart rate and systolic blood pressure at doses of 50, 150, and 400 mg/kg/min. There was a strong correlation between the magnitude of these effects and the logarithm of the steady-state blood concns. of esmolol. .