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), Vol. 12:3
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
QUINOLINES
BIOLOGICAL EFFECTS
SODIUM COMPOUNDS
MEMBRANE TRANSPORT
BRAIN
CARDIOVASCULAR AGENTS
DOSE-RESPONSE RELATIONSHIPS
GUINEA PIGS
MYOCARDIUM
NERVE CELLS
PYRIDINES
RATS
SODIUM 22
TRACER TECHNIQUES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
DRUGS
HEART
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MUSCLES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOISOTOPES
RODENTS
SODIUM ISOTOPES
SOMATIC CELLS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques