Leon I. Goldberg

Dopamine--clinical uses of an endogenous catecholamine.

THE third endogenous catecholamine, dopamine, has been extensively investigated in recent years. Dopamine, the immediate precursor of norepinephrine, is found in high concentrations in sympathetic ...

Effects of Dopamine in Man

Dopamine, the biochemical precursor of norepinephrine, was infused intravenously into 11 normal subjects and 2 patients. Results of hemodynamic studies in 6 normal subjects indicated that dopamine increased cardiac output and stroke volume in all subjects. Arterial pressure also increased in all subjects with a predominant systolic pressure increment. Calculated vascular resistance decreased in 5 subjects and did not change in the other subject. Changes in heart rate were of small magnitude and were inconstant in direction. Left atrial pressure did not change in 2 patients at a time when substantial increments in cardiac output were produced by dopamine. Comparison of the doses of dopamine and norepinephrine calculated to produce equivalent increments in systolic pressure indicated that dopamine was 1/25 to 1/56 as potent as norepinephrine in this respect. Infusions of dopamine produced relatively small but consistent increments in blood glucose levels. It is concluded that the pharmacological actions of dopamine in man are different from those of epinephrine and norepinephrine. Because of its distinctive properties, dopamine may be useful in the treatment of patients with inadequate cardiac output.

The Direct Effects of Norepinephrine, Epinephrine, and Methoxamine on Myocardial Contractile Force in Man

The effects of 5 sympathomimetic amines on myocardial contractile force were determined with the Walton-Brodie strain-gage arch in 16 patients undergoing operations for congenital heart disease. Equal doses of norepinephrine and epinephrine produced almost identical increments in myocardial contractile force; equipressor doses of methoxamine resulted in little or no change in the force of contraction. Mephentermine and metaraminol produced increments in myocardial contractile force similar to those following norepinephrine administration but the duration of action was longer. The results of these studies indicate that there are no qualitative differences in the actions of these amines on cardiac contractile force of dog and man and provide a basis for the rational clinical use of these agents.

Augmentation of Sodium and Potassium Excretion, Glomerular Filtration Rate and Renal Plasma Flow by Levodopa

Abstract After oral administration of levodopa in single doses of 1 to 2 g, glomerular filtration rate, renal plasma flow and sodium and potassium excretion significantly increased (p less than 0.05) in seven patients with Parkinsons disease. Similar effects were observed in patients initially treated with levodopa and in those receiving the drug for more than three months. Increased sodium and potassium excretion also occurred after administration of levodopa in three patients with congestive heart failure and in one with essential hypertension. The natriuretic effect of levodopa persisted for more than 150 minutes. These results suggest that the natriuretic effects of levodopa might be of value in the treatment of congestive heart failure. Natriuresis could also contribute to the orthostatic hypotension that commonly occurs in the levodopa-treated patient.

Selective depression of sympathetic transmission by intravenous administration of iproniazid and harmine.

Summary Large doses of iproniazid and harmine administered intravenously to the anesthetised cat and dog inhibit transmission through sympathetic ganglia without depressing the function of parasympathetic ganglia.

Effect of ring fluorination of epinephrine on its cardiovascular adrenoceptor activities

Effects of fluorine (F) substitution on the 2- and 6-positions of the catechol ring of epinephrine (Epi) on its alpha- and beta-adrenoceptor agonist activities were studied in anesthetized dogs. Increments in heart rate and contractile force were used as measures of beta 1-adrenoceptor activity, while increases and decreases in blood pressure and decreases and increases in femoral blood flow were used as measures of alpha- and beta 2-adrenoceptor activities, respectively. F substitution on the 2- and 6-positions of the catechol ring yielded compounds with opposite receptor selectivities: 2-FEpi was a selective beta-adrenoceptor agonist with little agonist activity at alpha-adrenoceptors, while the 6-F analog was a selective a-adrenoceptor agonist with no significant beta-adrenoceptor effects. Of added significance, 2-FEpi was more potent than Epi as a beta 1-adrenoceptor agonist, while 6-F Epi was more potent than the parent compound as an alpha-adrenoceptor agonist. The possible mechanisms for the effects of ring fluorination on the adrenoceptor activities of Epi and other sympathomimetic amines are discussed.