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Titolo:
A comparison of an A(1) adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig
Autore:
Snowdy, S; Liang, HX; Blackburn, B; Lum, R; Nelson, M; Wang, L; Pfister, J; Sharma, BP; Wolff, A; Belardinelli, L;
Indirizzi:
Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 Dept Med, Gainesville, FL 32610 USA Univ Florida, Coll Med, Dept Pharmacol, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 harmacol, Gainesville, FL 32610 USA CV Therapeut, Palo Alto, CA USA CV Therapeut Palo Alto CA USACV Therapeut, Palo Alto, CA USA Roche Biosci, Palo Alto, CA USA Roche Biosci Palo Alto CA USARoche Biosci, Palo Alto, CA USA Telik Inc, San Francisco, CA USA Telik Inc San Francisco CA USATelik Inc, San Francisco, CA USA
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 126, anno: 1999,
pagine: 137 - 146
SICI:
0007-1188(199901)126:1<137:ACOAAA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORONARY-ARTERY DISEASE; SUPRAVENTRICULAR TACHYCARDIA; ATRIOVENTRICULAR NODE; PHARMACOLOGY; ARRHYTHMIAS; DIAGNOSIS; TL-201;
Keywords:
adenosine; adenosine agonist; diltiazem; supraventricular tachycardia; re-entry; AV node; ventricular contractility; coronary vasodilation; action potential;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Belardinelli, L Univ,Florida, Coll Med, Dept Med, 1600 SW Archer Rd,Box 100277, Gainesville Univ Florida 1600 SW Archer Rd,Box 100277 Gainesville FL USA 32610
Citazione:
S. Snowdy et al., "A comparison of an A(1) adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig", BR J PHARM, 126(1), 1999, pp. 137-146

Abstract

1 The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A(1) adenosine receptor (A(1) receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-510), and the prototypical calcium channel blocker diltiazem.2 In the atrial-paced isolated heart, CVT-510 was approximately 5 fold more potent to prolong the stimulus-to-His bundle (S-H interval), a measure ofslowing AV nodal conduction (EC50 = 41 nM) than to increase coronary conductance (EC50 = 200 nM). At concentrations of CVT-510 (40 nM) and diltiazem (1 mu M) that caused equal prolongation of S-H interval (similar to 10 ms),diltiazem, but not CVT-510, significantly reduced left ventricular developed pressure (LVP) and markedly increased coronary conductance. CVT-510 shortened atrial (EC50 = 73 nM) but not the ventricular monophasic action potentials (MAP).3 In atrial-paced anaesthetized guinea-pigs, intravenous infusions of CVT-510 and diltiazem caused nearly equal prolongations of P-R interval. However, diltiazem, but not CVT-510, significantly reduced mean arterial blood pressure.4 Both CVT-510 and diltiazem prolonged S-H interval, i..e., slowed AV nodal conduction. However, the Al receptor-selective agonist CVT-510 did so without causing the negative inotropic, vasodilator, and hypotensive effects associated with diltiazem. Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 13:04:13