Document Detail


Antihypertensive effects of AT-112, a newly synthesized quinazoline derivative, in spontaneously hypertensive rats.
MedLine Citation:
PMID:  7480362     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to investigate the anti-hypertensive effect and possible mechanism of action of 2-(4-phenyl-1-piperazinyl)methyl-2,3-dihydroimidazo[1,2- c]quinazolin-5(6H)-one (AT-112), a newly synthesized ketanserin derivative, on in vivo and in vitro models. In vivo, central and peripheral administration of AT-112 produced a dose-dependent decrease of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). In in vitro study, the vasodilating effect of AT-112 on isolated thoracic aorta was endothelium-independent. AT-112 was found to be a potent alpha 1-adrenoceptor blocking agent in the rat thoracic aorta as revealed by its competitive antagonism of phenylephrine (pA2 = 9.82 +/- 0.19), but was found to have noncompetitive antagonism to 5-HT. The IC50 of ketanserin and AT-112 to phenylephrine were 27.8 nM and 0.36 nM, respectively, and to 5-HT were 5.73 nM and 0.44 microM, respectively. Competition binding studies demonstrated that the affinity of AT-112 to alpha 1-adrenoceptor (Ki = 2.01 +/- 0.09 nM) was significantly higher than that of alpha 2-adrenoceptor (Ki = 3.86 +/- 0.64 MM). Based on the results of these in vivo, in vitro and competition binding studies, AT-112 is a potent antihypertensive agent, and its antihypertensive action is mainly mediated by the blockade of the alpha 1-adrenoceptor.
Authors:
C J Tseng; S Y Chen; P L Tao; J W Chern; M H Yen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Science Council, Republic of China. Part B, Life sciences     Volume:  19     ISSN:  0255-6596     ISO Abbreviation:  Proc. Natl. Sci. Counc. Repub. China B     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1995-12-07     Completed Date:  1995-12-07     Revised Date:  2008-02-26    
Medline Journal Info:
Nlm Unique ID:  8502426     Medline TA:  Proc Natl Sci Counc Repub China B     Country:  TAIWAN    
Other Details:
Languages:  eng     Pagination:  159-65     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Antagonists / pharmacology
Animals
Antihypertensive Agents / therapeutic use*
Aorta, Thoracic / drug effects,  physiology
Binding, Competitive
Blood Pressure / drug effects
Clonidine / metabolism
Endothelium, Vascular / drug effects,  physiology
Female
Hypertension / drug therapy*
Male
Phenylephrine / antagonists & inhibitors,  pharmacology
Prazosin / metabolism
Quinazolines / pharmacology,  therapeutic use*
Rats
Rats, Inbred SHR
Serotonin / pharmacology
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/AT 112; 0/Adrenergic alpha-Antagonists; 0/Antihypertensive Agents; 0/Quinazolines; 19216-56-9/Prazosin; 4205-90-7/Clonidine; 50-67-9/Serotonin; 59-42-7/Phenylephrine

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


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