Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives
To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on /sup 22/Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance /sup 22/Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the /sup 22/Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs.
- Research Organization:
- Institut de Pharmacologie (UA 589 CNRS), Strasbourg (France)
- OSTI ID:
- 6464715
- Journal Information:
- J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States) Vol. 12:3; ISSN JCPCD
- Country of Publication:
- United States
- Language:
- English
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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
BRAIN
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GUINEA PIGS
HEART
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
MUSCLES
MYOCARDIUM
NERVE CELLS
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIDINES
QUINOLINES
RADIOISOTOPES
RATS
RODENTS
SODIUM 22
SODIUM COMPOUNDS
SODIUM ISOTOPES
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES