Investigation of the Positive Inotropic and Chronotropic Activities of a Number of Dopamine Derivatives

Dreyer, Anton C.

doi:10.1016/b978-0-08-021308-8.50283-0

Cited by 2 publications

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“…Recently the dopamine derivative dobutamine has been reported to possess positive inotropic selectivity (Tuttle, 1974). However, Dreyer (1975) reported that in virro studies with guinea-pig atria and strips revealed no inotropic selectivity of dobutamine, although in in siru experiments dobutamine showed a definite inotropic selectivity. In the present study, N-Gly-Gly-Leudopamine induced predominant inotropic effects in the isolated dog atrium preparation, but another six amino acid conjugated derivatives of dopamine induced both positive chronotropic and inotropic effects corresponding to those of dopamine throughout the range of doses studied.…”

Section: S Chibamentioning

confidence: 98%

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Comparative Study of Chronotropic and Inotropic Effects of Dopamine and Seven Derivatives on the Isolated, Blood‐perfused Dog Atrium

Chiba

1978

Clin Exp Pharma Physio

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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.

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Section: S Chibamentioning

confidence: 98%

“…Recently, many dopamine derivatives were synthesized and pharmacologically investigated for their potential clinical applications (Biel et al, 1973;Tuttle, 1974;Dreyer, 1975;Jewitt et ul., 1975;Loeb et ul., 1975).…”

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Comparative Study of Chronotropic and Inotropic Effects of Dopamine and Seven Derivatives on the Isolated, Blood‐perfused Dog Atrium

Chiba

1978

Clin Exp Pharma Physio

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“…Recently, several dopamine derivatives were synthesized and were found to protect the molecule at its metabolically vulnerable sites (8)(9)(10)(11)(12). In the present study, secretory re sponses to dopamine and seven amino acid conjugated derivatives of dopamine were com pared, using the blood-perfused dog pancreas preparation.…”

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confidence: 99%

Local Anesthetic Activity of β-Adrenergic Blocking Drugs in the Crayfish Giant Axon, with Reference to Calcium Ion

Iwatsuki

Chiba

1980

Japanese Journal of Pharmacology

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Abstract-The secretory responses to seven dopamine amino acid conjugated derivatives were compared with those to dopamine, using blood-perfused canine pancreas pre parations. Each of these dopamine derivatives produced a dose dependent increase in the secretion of pancreatic juice. The rank order of the secretory responses and relative potency (dopamine =1) was: N-Ileu-dopamine (0.4)>N-Ala-Glu-dopamineThe duration of action of doses of the derivatives which produced approximately equal secretory responses was about 1.22.7 times longer than that of dopamine. Dopamine and N-Ileu-dopamine which has the most potent secretagogue property among seven dopamine derivatives produced a secretin-like secretion of the pancreatic juice con taining a high concentration of bicarbonate but had little effect on protein output with lower amylase activity.Dopamine is a precursor of noradrenaline and has characteristics which form other catecholamines, on systemic blood pressure (1, 2), in the renal or mesenteric vascular bed (1, 3) and in the coronary circulation (4). These effects of dopamine may be the result of actions on specific dopamine receptors (5).It has been reported that dopamine produced an increase in the secretion of pancreatic juice in dogs but that noradrenaline had no effect on pancreatic secretion (6). As the secretagogue effect of dopamine was antagonized by haloperidol it was suggested that there were specific dopamine receptors in the dog pancreas (7).Recently, several dopamine derivatives were synthesized and were found to protect the molecule at its metabolically vulnerable sites (8-12). In the present study, secretory re sponses to dopamine and seven amino acid conjugated derivatives of dopamine were com pared, using the blood-perfused dog pancreas preparation.Moreover, we attempted to determine among the seven dopamine derivatives, compositions of the pancreatic juice induced by secretin, dopamine and N-lieu-dopamine which had the most potent secre tagogue properties. MATERIALS AND METHODSTen mongrel dogs of either sex, weighing from 44 to 17 kg, were fasted for 24 hr and anaesthetized with sodium pentobarbital (30 mg/kg, i.v.). During the experimental pro

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Investigation of the Positive Inotropic and Chronotropic Activities of a Number of Dopamine Derivatives

Cited by 2 publications

References 0 publications

Comparative Study of Chronotropic and Inotropic Effects of Dopamine and Seven Derivatives on the Isolated, Blood‐perfused Dog Atrium

Comparative Study of Chronotropic and Inotropic Effects of Dopamine and Seven Derivatives on the Isolated, Blood‐perfused Dog Atrium

Local Anesthetic Activity of β-Adrenergic Blocking Drugs in the Crayfish Giant Axon, with Reference to Calcium Ion

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