Document Detail


Studies with abanoquil (UK-52,046) a novel quinoline alpha 1-adrenoceptor antagonist: II. Duration of action, pharmacokinetics and concentration-effect relationships in normotensive subjects.
MedLine Citation:
PMID:  1683250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. This study further examines the quinoline-derivative abanoquil with particular respect to the duration of its alpha 1-adrenoceptor antagonist activity and its concentration-effect relationship following a single intravenous bolus dose of 0.5 micrograms kg-1 in young, normotensive males. 2. alpha 1-adrenoceptor antagonism (as assessed by phenylephrine pressor responses) was detectable for up to 12 h post dosing: at 12 h there was a significant 1.5-fold rightward shift (95% CI: 2.2 to 1.1) of the pressor dose-response curve for diastolic blood pressure. 3. Despite evidence of substantial alpha 1-adrenoceptor antagonism abanoquil had no significant effect on blood pressure, supine and erect, but there were small and statistically significant increments in heart rate. 4. The degree of alpha 1-adrenoceptor antagonism was related to whole blood concentrations abanoquil: the PD-ratios of phenylephrine pressor responses performed at 1, 6, and 12 h post dosing were significantly correlated with log drug concentrations (r = 0.57 for systolic (P less than 0.05) and r = 0.78 for diastolic blood pressure (P less than 0.005). 5. In conclusion, abanoquil produced significant alpha 1-adrenoceptor antagonism which was related to circulating drug concentrations. The absence of other significant cardiovascular effects suggests that abanoquil warrants further clinical study as an antiarrhythmic agent.
Authors:
R F Schafers; H L Elliott; P A Meredith; S H Miller; J L Reid
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  32     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  1991 Nov 
Date Detail:
Created Date:  1991-12-30     Completed Date:  1991-12-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  605-10     Citation Subset:  IM    
Affiliation:
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Antagonists / blood,  pharmacokinetics*,  pharmacology
Adult
Aminoquinolines / blood,  pharmacokinetics*,  pharmacology
Blood Pressure / drug effects*
Dose-Response Relationship, Drug
Heart Rate / drug effects
Humans
Injections, Intravenous
Male
Phenylephrine / antagonists & inhibitors,  pharmacology
Single-Blind Method
Tetrahydroisoquinolines*
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Aminoquinolines; 0/Tetrahydroisoquinolines; 118931-00-3/abanoquil; 59-42-7/Phenylephrine
Comments/Corrections

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