Comparative study of chronotropic and inotropic effects of dopamine and seven derivatives on the isolated, blood-perfused dog atrium.
1. The effects of seven dopamine amino acid conjugated derivatives were compared with those of dopamine on sinus rate and contractile force using the isolated, blood-perfused dog atrium preparation. 2. Each of these dopamine derivatives induced dose-related positive chronotropic and inotropic effects. 3. The positive chronotropic and inotropic effects were obtained with the same rank order of potency for each effect with six of the dopamine derivatives. Their rank order and relative potency (dopamine = 1000) were: N-Ileu-dopamine (3) greater than N-Glu-Pro-dopamine (1) = N-Ala-Glu-dopamine (1) greater than N-Gly-Gly-dopamine (0.3) = N-gamma-Glu-dopamine (0.3) greater than N-Gly-Gly-Leu-dopamine (0.1) greater than N-Gly-Gly-Pro-dopamine (0.01). 4. In doses producing equal positive inotropic effects, the positive chronotropic effect of N-Gly-Gly-Leu-dopamine was much less than with the other derivatives tested. Its potency compared to dopamine (= 1000) was 0.3 for the inotropic and 0.1 for the chronotropic effect. 5. The duration of action of doses of the derivatives producing approximately equal positive inotropic responses was in the order N-Ileu-dopamine = N-gamma-Glu-dopamine = N-Gly-Pro-dopamine = N-Ala-Glu-dopamine greater than N-Gly-Gly-dopamine = N-Gly-Gly-Leu-dopamine = N-Gly-Gly-Pro-dopamine greater than dopamine.
D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D013268:Stimulation, Chemical
D004298:Dopamine