Document Detail


Cardiovascular effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl ester.
MedLine Citation:
PMID:  1530674     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardiovascular effects of 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or open-chest dogs and Langendorff perfused rabbit hearts, and compared with those of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with a fall in mean blood pressure (MBP). These effects were nearly equipotent with those of NF and NC, but more durable. A similar effect was obtained by intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while cardiac output (CO) and stroke volume (SV) increased without apparent changes in heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 were equipotent with NF and NC, whereas increases in CO and SV were more potent than those of the two drugs. These actions of NP-252 were longer than those of the reference agents. Further, in perfused rabbit hearts, NO-252 increased coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its effect in CPF was equipotent with NF and 2 times less than that of NC, however the duration was much longer than those of the reference drugs. On the other hand, the negative inotropic effect of NP-252 was less than NF, but greater than that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened atrio-His bundle conduction time, without affecting His bundle-ventricular conduction time. Lengthening effect of NP-252 was about 4 times less than that of NF. These results suggest that NP-252 acts more selectively on vascular smooth muscle than cardiac muscle, and has almost equipotent but markedly longer vasodilating actions as compared to NF and NC. It may be expected that NP-252 is a new generation of tissue specific and long acting Ca2+ antagonist.
Authors:
M Hojo; N Teramoto; H Hata; O Katayama; H Tatsumi; S Shibata
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  42     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1992 May 
Date Detail:
Created Date:  1992-10-20     Completed Date:  1992-10-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  621-8     Citation Subset:  IM    
Affiliation:
Pharmacological Department, Nippon Shoji Kaisha, Ltd., Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Calcium Channel Blockers / pharmacology*
Coronary Circulation / drug effects
Dihydropyridines / pharmacology*
Dogs
Female
Heart Conduction System / drug effects
Hemodynamics / drug effects*
Male
Nicardipine / pharmacology
Nifedipine / pharmacology
Rabbits
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Dihydropyridines; 0/Vasodilator Agents; 132031-81-3/NP 252; 21829-25-4/Nifedipine; 55985-32-5/Nicardipine

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