Norepinephrine (medication)

About: Norepinephrine (medication) is a research topic. Over the lifetime, 12189 publications have been published within this topic receiving 371139 citations. The topic is also known as: Norepinephrine bitartrate & Norepinephrine (drug).

Dobutamine: development of a new catecholamine to selectively increase cardiac contractility.

Abstract: We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on beta1 cardiac receptors. However, unlike epinephrine, dobutamine's effect on alpha and beta2 vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethylimipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, cuased extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure.

A concept for a role of serotonin and norepinephrine as chemical mediators in the brain.

Abstract: It is not the purpose of this paper to make a survey of the work suggesting that serotonin is a central neurohumoral agent, since much of this is being discussed by other contributors to this monograph. Rather, we should like to offer a concept that implicates serotinon and norepinephrine as chemical mediators of mutally antagonistic centers in the brain. This thesis, which is admittedly oversimplified, endeavors to explain the actions of the tranquilizing agents reserpine and chlorpromazine and the hallucinogenic agents LSD and mescaline in terms of interactions with serotonin and norepinephrine in the central nervous system. As presented here this concept may begin to trace the outlines of a coherent picture, but one, we are sure, that will bear only a faint resemblance to the picture that will ultimately emerge. The concept is only a working hypothesis, but i t has already proved useful in linking a number of unrelated observations and in suggesting certain experiments that might test it. It is fascinating to learn how the discovery of serotonin, a substance that appears to have no part in the general metabolism of cells, has proved to be of such significance to the pharmacologist, the biochemist, the neurophysiologist and, possibly, to the psychiatrist. When the vasoconstrictive material in blood platelets was finally isolated and identified as 5-hydroxytryptaminel1, i t was soon proved identical with the enteramine that Erspamer3 had extracted years before from the gastrointestinal tracts of the vertebrates and from other organs in the invertebrates. A number of notions concerning its role in the body were considered, most of which took into account its profound contractive action on smooth muscle. Among these possibilities were the control of vascular tone and, therefore, of systemic blood pressure; control of gastrointestinal motility; regulation of water excretion by affecting kidney arterioles; and regulation of hemostatic action by affecting blood vessels after release from platel e t ~ . ~ . Several of these suggestions can be more or less summarily dealt with a t once. Since serotonin is normally present in the body almost entirely in a bound and therefore presumably inactive form, i t is doubtful that there is enough of the free form circulating in plasma to affect the vascular tone either of the body as a whole or of the kidneys in particular. Results from our laboratory indicate that it is not involved in any obvious way in hemostasis, since animals and humans whose platelets have been depleted of serotonin by the administration of reserpine show no change in bleeding or clotting time.6 It is possible that serotonin controls some aspects of gastrointestinal motility, although no direct evidence is as yet forthcoming in this connection. The clue pointing to a role for serotonin in the functioning of the central

Plasma catecholamines and essential hypertension. An analytical review.

Abstract: Of 78 comparative studies of plasma catecholamines in patients with essential hypertension and in normotensive controls, most reported higher catecholamine levels in the hypertensives, although only about 40% of the studies were positive (reporting statistically significant hypertensive-normotensive differences). Although there was dramatic variability in catecholamine values within and across studies, virtually all studies of norepinephrine in young, consistently hypertensive patients were positive. The likelihood that a study was positive with respect to norepinephrine was independent of the likelihood with respect to epinephrine, so that total catecholamine values, or else the sum of norepinephrine plus epinephrine, differentiated hypertensives from normotensives to a greater extent than levels of either substance alone. The preponderance of literature on the subject supports the hypothesis that increased plasma catecholamine concentrations occur in some patients with essential hypertension. Elevated plasma norepinephrine in relatively young, established hypertensive patients is consistent with a pathophysiologic role for increased sympathetic neural activity in this subgroup.

The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat

Abstract: Important contributions towards our present understanding of sympathetic nerve-smooth muscle traismission have come from studies with innervated preparations of organs such as the nictitating membrane, vas deferens and intestine. Studies on the control of the circulation by the sympathetic nervous system have been more limited. In this paper a comparatively simple innervated preparation of perfused mesenteric blood vessels is described in which the vessels are severed close to the intestine to avoid confusion between the activity of vascular and intestinal smooth muscle. With this preparation the actions and interactions of sympathetic nerve stimulation and drugs on the mesenteric blood vessels can be readily investigated. The operative procedures required for setting up the preparation can be completed within 30 min.