Document Detail


Integrative cardiovascular actions of a novel catecholamine, GP-2-128.
MedLine Citation:
PMID:  7515995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Systematic modification in the chemical structure of dobutamine resulted in production of a long-acting, highly potent catecholamine, GP-2-128 [(1-(3,4-dihydroxyphenyl)-2-[3-(4-carbamyl phenyl)-1-methylpropylamino] ethanol)]. The cardiovascular actions of GP-2-128 were compared with those of isoproterenol (ISO) and dobutamine (DOB) in anesthetized dogs. GP-2-128 significantly increased left ventricular pressure (LVdP/dtmax), cardiac output (CO), and heart rate (HR). It also reduced total peripheral vascular resistance (TPVR). For a given increase in contractility, changes in HR were greater after ISO than after GP-2-128 administration. DOB did not change HR significantly. Both GP-2-128 and DOB reduced TPVR, but ISO was more effective than GP-2-128 and DOB in reducing TPVR. GP-2-128 was 18,000 and 52 times more potent than DOB and ISO, respectively, in increasing LVdP/dtmax. For a given increase in contractility, the cardiovascular actions of GP-2-128 lasted significantly longer than those of DOB or ISO. A 50% mixture of the RR and RS distereoisomer forms of GP-2-128 (GP-2-114) have the same pharmacologic profile as the pure RR distereoisomer. Both GP-2-128 and GP-2-114 produced current-dependent cardiovascular actions when administered by transdermal iontophoresis. The inotropic and chronotropic effects of GP-2-128 are both largely due to stimulation of beta-adrenoceptors, as shown by receptor blockade with propranolol. GP-2-128 is a very potent, long-acting catecholamine that can be administered by other than intravenous (i.v.) route.
Authors:
G Abou-Mohamed; R W Caldwell; T M Ibrahim; R R Tuttle
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  23     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-07-11     Completed Date:  1994-07-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  485-91     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology
Animals
Benzamides / administration & dosage,  pharmacology*
Cardiac Output / drug effects
Cardiovascular Agents / administration & dosage,  pharmacology*
Catecholamines / administration & dosage,  pharmacology*
Dobutamine / pharmacology
Dogs
Female
Half-Life
Heart Rate / drug effects
Hemodynamics / drug effects*
Injections, Intravenous
Iontophoresis
Isoproterenol / pharmacology
Male
Muscle Contraction / drug effects
Myocardial Contraction / drug effects
Stereoisomerism
Vascular Resistance / drug effects
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Benzamides; 0/Cardiovascular Agents; 0/Catecholamines; 130783-39-0/1-(3,4-dihydroxyphenyl)-2-(3-(4-carbamylphenyl)-1-methylpropylamino)ethanol; 34368-04-2/Dobutamine; 7683-59-2/Isoproterenol

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


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