Cardiovascular Effects and Plasma Levels of Denopamine (TA-064), a New Positive Inotropic Agent, in Chronically Instrumented Dogs
Open Access
- 1 January 1985
- journal article
- research article
- Published by Elsevier in The Japanese Journal of Pharmacology
- Vol. 39 (2), 191-193
- https://doi.org/10.1254/jjp.39.191
Abstract
Cardiovascular effects of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs were investigated following intravenous and oral administration. In the conscious state, denopamine (0.5-4 μg/kg/min, i.v. infusion) increased LV dp/dtmax, cardiac output, stroke volume in a dose-dependent manner, and it decreased left ventricular end-diastolic pressure, total peripheral resistance and PQ interval. Denopamine produced an increase in LV dp/dtmax by 90% at a rate of 4 μg/kg/min with slightly increasing systemic blood pressure and heart rate. In the same dogs after anesthetizing with pentobarbital, denopamine in the same dose range showed more marked positive inotropic effects and less changes in cardiac output and total peripheral resistance than in conscious dogs. Other cardiovascular effects of denopamine were qualitatively similar to conscious dogs. These effects of denopamine were diminished by treatment with propranolol. Oral administration of denopamine to conscious dogs (0.1-0.4 mg/kg) produced a rise in LV dp/dtmax dose-dependently, and denopamine at a dose of 0.4 mg/kg increased LV dp/dtmax by 66%, this effect lasting for 7 hr. Heart rate and blood pressure were not affected significantly. Effects on other cardiovascular parameters were changed in the same direction as intravenous administration. The increase in LV dp/dtmax corresponded well with the changes in plasma levels of denopamine in conscious dogs by both intravenous and oral administration. Denopamine showed a selective positive inotropic effect in chronically instrumented dogs, and its positive inotropic action was more marked in the myocardium depressed with an anesthetizing dose of pentobarbital than in the conscious state.This publication has 8 references indexed in Scilit:
- Cardiovascular Effects of a New Positive Inotropic Agent, (−)-(R)-1-(p-Hydroxyphenyl)-2-[(3,4-Dimethoxyphenethyl) Amino]-Ethanol (TA-064) in the Anesthetized Dog and Isolated Guinea Pig HeartThe Japanese Journal of Pharmacology, 1983
- Cardiovascular effects of a newly synthesized cardiotonic agent (TA-064) on normal and diseased heartsThe American Journal of Cardiology, 1983
- METABOLISM OF A NEW CARDIOTONIC AGENT, (-)-ALPHA-(3,4-DIMETHOXYPHENETHYLAMINOMETHYL)-4-HYDROXYBENZYL ALCOHOL (TA-064), IN MAN - O-DEMETHYLATION AND RING HYDROXYLATION1983
- Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulationAmerican Journal of Physiology-Legacy Content, 1971
- Hemodynamic alterations after 30 minutes of pentobarbital sodium anesthesia in dogsAmerican Journal of Physiology-Legacy Content, 1964
- Effects of Sodium Pentobarbital on Electrical and Reflex Activation of the Cardiovascular SystemCirculation Research, 1964
- General Anesthesia and Circulatory HomeostasisPhysiological Reviews, 1960
- Cardiovascular Effects of Anesthetic Doses of Pentobarbital SodiumAmerican Journal of Physiology-Legacy Content, 1956