Document Detail


Beta-adrenoreceptor antagonist potency and pharmacodynamics of ASL-8123, the primary acid metabolite of esmolol.
MedLine Citation:
PMID:  2452313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The beta-adrenoreceptor antagonist properties of ASL-8123, the primary metabolite of esmolol, were determined in vitro and in vivo. ASL-8123 demonstrated weak competitive beta-adrenoreceptor blocking activity in isolated guinea pig right atria with a pA2 of 3.73 +/- 0.07; no agonist-like activity was observed in this tissue at concentrations of ASL-8123 from 3 X 10(-5) to 1 X 10(-2) M. In anesthetized dogs, ASL-8123 was infused at increasing dosages from 0.2-25.6 mg/kg/min, each dose rate maintained for 20 min. The compound produced a slight decrease in heart rate of 15-22 beats/min at cumulative doses of 508-1,020 mg/kg and decreased diastolic blood pressure by 14-47 mm Hg at cumulative doses of 252-1,020 mg/kg. ASL-8123 dose-dependently inhibited the heart rate and diastolic blood pressure responses to isoproterenol (0.5 micrograms/kg i.v.). Blood levels of ASL-8123 were linearly correlated with inhibition of the heart rate response to isoproterenol (r = 0.95-0.99 for each dog, n = 6). The blood level of ASL-8123 that produced a 50% inhibition of isoproterenol-induced tachycardia averaged 293 +/- 65 micrograms/ml. Recovery from beta-adrenoreceptor blockade after terminating the infusion of ASL-8123 occurred slowly, decreasing from 81% at the end of the infusion to 55% 60 min later, and was paralleled by a slow decrease in blood levels of ASL-8123. Thus, ASL-8123 is a weak beta-adrenoreceptor antagonist which is approximately 1,600-1,900 times less potent than its parent, esmolol.
Authors:
J E Shaffer; C Y Quon; R J Gorczynski
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  11     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1988 Feb 
Date Detail:
Created Date:  1988-05-27     Completed Date:  1988-05-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  187-92     Citation Subset:  IM    
Affiliation:
Du Pont Critical Care, Department of Pharmaceutical Research, Waukegan, Illinois.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists* / pharmacokinetics
Animals
Blood Pressure / drug effects
Dogs
Female
Guinea Pigs
Heart Rate / drug effects
Infusions, Intravenous
Isoproterenol / antagonists & inhibitors
Male
Propanolamines / pharmacokinetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Propanolamines; 7683-59-2/Isoproterenol; 81148-15-4/ALS 8123

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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