Document Detail


Pharmacological properties of 5-[(6,7,8-trimethoxy-4-quinazolinyl) amino]-1-pentanyl nitrate maleate in cardiovascular system.
MedLine Citation:
PMID:  1815519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Effects of 5-[6,7,8-trimethoxy-4-quinazolinyl)amino]-1-pentanyl nitrate maleate (KT-1, CAS 47487-05-8), whose chemical structure has both a prazosin and a nitrate moiety, on cardiovascular system were investigated in in vivo and in vitro experiments. KT-1 i.v. decreased aortic pressure, renal blood flow, left ventricular enddiastolic pressure and resistances of total peripheral, vertebral, coronary and renal vasculatures and increased aortic blood flow, vertebral blood flow, coronary blood flow, peak positive left ventricular dP/dt and heart rate in anesthetized open-chest dogs. These cardiovascular effects of KT-1 were similar to those of glyceryl trinitrate (nitroglycerin, GTN). Nitrate-deleted KT-1 from its chemical structure (denitro KT-1) equimolar to KT-1 produced no marked changes in these cardiovascular parameters, but 3 or 10 times large doses of denitro KT-1 showed relatively long persisting vasodilator effects. In isolated dog coronary artery preparations contracted with KCl, the order of relaxant potency was GTN greater than KT-1 greater than denitro KT-1. In isolated dog mesenteric artery preparations, phenylephrine produced concentration-dependent contractions which were significantly inhibited by prazosin and KT-1 but not by denitro KT-1. In anesthetized open-chest dogs, phenylephrine produced pressor responses which were significantly inhibited by KT-1 but not by GTN or denitro KT-1. In isolated rat thoracic aorta strips, in contrast to GTN, KT-1 hardly developed a tachyphylaxis. Thus, KT-1 showed cardiovascular effects similar to those of both nitrates and a1-adrenoceptor blocking agents with no development of a tachyphylaxis.
Authors:
Y Miyamoto; K Noguchi; J Nakasone; M Sakanashi
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  41     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1991 Dec 
Date Detail:
Created Date:  1992-06-23     Completed Date:  1992-06-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1216-21     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / drug effects
Blood Pressure / drug effects
Cardiovascular Agents / pharmacology*
Cardiovascular System / drug effects*
Coronary Vessels / drug effects
Dogs
Endothelium, Vascular / drug effects
Female
Heart Rate / drug effects
Male
Muscle, Smooth, Vascular / drug effects
Nitro Compounds / pharmacology*
Nitroglycerin / pharmacology
Norepinephrine / pharmacology
Phenylephrine / pharmacology
Prazosin / pharmacology
Quinazolines / pharmacology*
Rats
Rats, Inbred Strains
Regional Blood Flow / drug effects
Vascular Resistance / drug effects
Chemical
Reg. No./Substance:
0/Cardiovascular Agents; 0/Nitro Compounds; 0/Quinazolines; 19216-56-9/Prazosin; 33371-02-7/denitro-KT-1; 47487-05-8/KT 1; 51-41-2/Norepinephrine; 55-63-0/Nitroglycerin; 59-42-7/Phenylephrine

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


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