Showing papers on "Norepinephrine (medication) published in 2011"

Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study.

Abstract: Objective:There is no study that has compared, in a randomized manner, which vasopressor is most suitable in optimizing both systemic and regional hemodynamics in cardiogenic shock patients. Hence, the present study was designed to compare epinephrine and norepinephrine-dobutamine in dopamine-resist

Inhibition of noradrenaline uptake by drugs.

Abstract: Sm,-The in vivo studies of Axelrod, Whitby & Hertting (1961), Hertting, Axelrod & Whitby (1961), Hertting, Axelrod & Patrick (1962) and Axelrod, Hertting & Potter (1962) and the in v i m studies of Dengler, Spiegel & Titus (1961) showed that the uptake of noradrenaline into sympathetically innervated tissues can be inhibited by a wide variety of drugs. Among the compounds reported to act as inhibitors of noradrenaline uptake were cocaine, reserpine, guanethidine, imipramine, chlorpromazine and the adrenergic blocking agents dichloroisoprenaline (DCI), ergotamine and phenoxybenzamine. The present study was undertaken as a quantitative investigation of the potencies of these and certain other drugs as inhibitors of noradrenaline uptake. In previous reports from this laboratory the kinetics of noradrenaline uptake in the isolated perfused rat heart and the inhibition of this process by a group of sympathomimetic amines have been described (Iversen, 1963 ; 1964). The methods used in the present experiments are described in these papers. Drugs were added to the perfusing medium, which also contained 14C-noradrenaline. The uptake of noradrenaline was measured by analysing the '*C-noradrenaline content of the heart at the end of a 10 min. perfusion. Each drug concentration was tested on a group of four hearts and the results were expressed as the mean percentage inhibition of noradrenaline uptake in the drug-treated group when compared with the uptake in drug-free controls. When sufficient data were available the drug concentration required to produce a 50% inhibition of noradrenaline uptake (ID50) was calculated.

Histochemical amd biochemical effects of diethyldithiocarbamate on tissue catecholamines

Abstract: Histochemical amd biochemical effects of diethyldithiocarbamate on tissue catecholamines SIR,-Recently diethyldithiocarbamate, an inhibitor of dopamine-p-oxidase, has been found to cause a decrease in noradrenaline and an increase in dopamine in rat ileum (Collins, 1965). The present study was planned to elucidate this effect further by means of a combined histochemical and biochemical approach. Some male, albino, Sprague-Dawley rats (200-300 g) were treated with a single dose of 500 mg/kg S.C. of diethyldithiocarbamate (calculated as the sodium salt with 3 molecules of water of crystallisation) and killed at various intervals after the injection, while others received 2 doses of 500 mg/kg s.c., 7 and 3-4 hr before death. The brain, heart, submaxillary and adrenal glands, small intestine and femoral muscle were examined. Some animals were taken for the biochemical assay of dopamine (Carlsson & Waldeck, 1958 ; Carlsson & Lindqvist, 1962) and noradrenaline (Bertler, Carlsson & Rosengren, 1958). Others were taken for histochemical analysis (Falck, Hillarp, Thieme & Torp, 1962; Falck, 1962; Hillarp, Fuxe & Dahlstrom, 1965).

The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans.

Abstract: This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.

Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients.

Abstract: Objective:To assess the effects of norepinephrine on cardiac preload, cardiac index, and preload dependency during septic shock.Design:Prospective interventional study.Setting:Medical Intensive Care Unit.Patients:We included 25 septic shock patients (62 ± 13 yrs old, Simplified Acute Physiology Scor

Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury

Abstract: Purpose The use of norepinephrine (NE) in patients with volume-resuscitated vasodilatory shock and acute kidney injury (AKI) remains the subject of much debate and controversy. The effects of NE-induced variations in mean arterial blood pressure (MAP) on renal blood flow (RBF), oxygen delivery (RDO2), glomerular filtration rate (GFR) and the renal oxygen supply/demand relationship (renal oxygenation) in vasodilatory shock with AKI have not been previously studied.

In Vivo Comparison of Norepinephrine and Dopamine Release in Rat Brain by Simultaneous Measurements with Fast-Scan Cyclic Voltammetry

Abstract: Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. In this study, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle, the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra, the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode fast-scan cyclic voltammetry technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures.

Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine.

Abstract: Objective:To evaluate to which extent the systemic arterial pulse pressure could be used as a surrogate of cardiac output for assessing the effects of a fluid challenge and of norepinephrine.Design:Observational study.Setting:Medical intensive care unit.Patients:Patients with an acute circulatory fa

Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.

Abstract: Background Sympathetic overactivity and catecholamine accumulation are important characteristic findings in heart failure, which contribute to its pathophysiology. Here, we identify a potential mechanism underlying norepinephrine accumulation in a rat model of heart failure.

Inhibition of noradrenaline uptake by sympathomimetic amines.

Abstract: SIR,-The uptake of noradrenaline into tissues innervated by the sympathetic nervous system can be inhibited by a wide variety of drugs (Whitby, Hertting & Axelrod, 1960; Axelrod, Whitby & Hertting, 1961 ; Hertting, Axelrod & Whitby, 1961 ; Dengler, Spiegel & Titus, 1961 ; Axelrod, Hertting & Potter, 1962). Some of these inhibitors such as the sympathomimetic amines tyramine, amphetamine and ephedrine are closely related chemically to noradrenaline, and the present study was undertaken as a systematic and quantitative investigation of the inhibition of noradrenaline uptake by these and other chemically related amines to elucidate the structural specificity of the noradrenaline uptake site. Rat hearts were perfused by the Langendorff technique with a medium containing DL-P14C-noradrenaline (specific activity = 130pc/mg) at a concentration of 10 ng/ml. The uptake of noradrenaline was measured by assaying the tissue content of l*C-noradrenaline at the end of a 10 min perfusion. The methods used for measuring the uptake of radioactively-labelled noradrenaline in this preparation have been described in detail elsewhere (Iversen, 1963). Drugs were added A simple test procedure has been designed for this purpose.

A molecular basis for drug action. the interaction of one or more drugs with different receptors.

Abstract: Non-competitive interaction is the interference by a drug B with the action of a drug A, both drugs acting on different, but interrelated receptors, while drug B is inactive if applied alone and only modifies the action of a second drug, A. This type of interaction can be put into a formula based on the mass-action law (eqn 1 is an example). The second term in this equation determines the change in the effect of drug A brought about by drug B. E

The effect of amantadine on the uptake of dopamine and noradrenaline by rat brain homogenates.

Abstract: Amantadine hydrochloride (1-adamantanamine hydrochloride), an antiviral agent (Davies, Grunert & others, 1964) has been shown to be effective against parkinsonism (Schwab, England, & others 1969, Parkes, Calver & others, 1970). The mode of action of the drug in improving the condition of the parkinsonian patient has not been elucidated. The results of Vernier, Harmon & others (1969) suggested that, in high doses, amantadine inhibits the uptake of noradrenaline into peripheral nerve endings. It seemed reasonable to suppose that a similar action on the uptake of dopamine into central neurons might, in part, explain the anti-parkinsonian activity of amantadine. To investigate this possibility, preliminary experiments have been performed using a method based on that described by Snyder & Coyle (1969). Fresh rat brain was homogenized in 10 volumes of oxygenated (95% 02, 5% CO,) modified Krebs-Henseleit buffer pH 7-2, using a "Tri-R' tissue homogenizer with a teflon pestle and a clearance of 0.15-0.23 mm at 750 rev/min. After further oxygenation, 1 ml aliquots of the homogenate were placed in small lengths of 4 inch dialysis tubing, tied at both ends to form a sac containing an air bubble to aid mixing. The sacs were placed in stoppered test-tubes containing 5.0 ml Krebs-Henseleit buffer pH 7.2, and were incubated, with constant mixing, at 37". At the start of each experiment, either dopamine or noradrenaline was added to the external medium, in a concentration of 1.0 pg/ml. In each case, 0.05 Ci/ml of [14C]labelled amine was included in the total concentration. To measure amine uptake, the contents of the dialysis bag were first centrifuged at 48 000 g and 0.2 ml of the supernatant fluid was added to 15 ml of Scintillation fluid (1 litre toluene: 500ml methanol: 5 g POPOP: 0.1 g PPO). The pellet was digested in 3 ml M Hyamine solution, and 0.2 ml of the digest was added to 15 ml of scintillation fluid. The number of disintegrations in 10 min at 7" were recorded using a Packard liquid scintillation counter. While the increase in radioactivity in the supernatant, caused by passive diffusion of the amine, rapidly reached a maximum, radioactivity in the pellet reached a maximum after 2 h. Uptake of amines into the pellet was shown to be sodium dependent and temperature dependent, and was inhibited by ouabain (see Fig. 1 Aand B) ; it was therefore assumed to involve an active process. The inclusion in the homogenate and incubating medium of various concentrations of reserpine did not reduce the radioactivity in the pellet by more than 40% and it was further assumed that the uptake which was reserpineresistant represented active uptake into intact nerve endings. Fig. 1A shows the effect of amantadine, added to the medium and to the homogenate, on the uptake of noradrenaline into nerve endings. A concentration of 1 x 10-4g/ml decreased the radioactivity in the pellet by 87%. Concentration between 1 x and 5 x Fig. 1B shows the effect of amantadine on dopamine uptake. All concentrations between 1 x g/ml produced a similar reduction in uptake of 3852%. A concentration of 1 x was required to produce an inhibition of 69%. If it is assumed that the 40% of the total uptake inhibited by reserpine represents active uptake into synaptic vesicles released by homogenization, then our experiments have not excluded the possibility that amantadine will inhibit the uptake of dopamine and noradrenaline by this process. However, it seems more likely that this reduction in radioactivity represents a non-specific action, probably on passive diffusion, since it was readily produced by widely-varying concentrations of several drugs, including reserpine and amantadine. What does emerge clearly from our results is that, under the conditions of our experiments, high concentrations of amantadine are required to produce significant 957

Hypotension during Fluid-restricted Abdominal Surgery: Effects of Norepinephrine Treatment on Regional and Microcirculatory Blood Flow in the Intestinal Tract

Abstract: Vasopressors, such as norepinephrine, are frequently used to treat perioperative hypotension. Increasing perfusion pressure with norepinephrine may increase blood flow in regions at risk. However, the resulting vasoconstriction could deteriorate microcirculatory blood flow in the intestinal tract and kidneys. This animal study was designed to investigate the effects of treating perioperative hypotension with norepinephrine during laparotomy with low fluid volume replacement.

Effects of Norepinephrine Treatment on Regional and Microcirculatory Blood Flow in the Intestinal Tract

Abstract: Background: Vasopressors, such as norepinephrine, are frequently used to treat perioperative hypotension. Increasing perfusion pressure with norepinephrine may increase blood flow in regions at risk. However, the resulting vasoconstriction could deteriorate microcirculatory blood flow in the intestinal tract and kidneys. This animal study was designed to investigate the effects of treating perioperative hypotension with norepinephrine during laparotomy with low fluid volume replacement. Methods: Twenty anesthetized and ventilated pigs were randomly assigned to a control or treatment (norepinephrine) group. Both groups received 3 ml kg 1 h 1 Ringer’s lactate solution. In addition, the norepinephrine group received norepinephrine to stepwise increase blood pressure to 65 and 75 mmHg. Regional blood flow was measured in the splanchnic arteries. In the small bowel and colon, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes. Results: Hepatosplanchnicandkidneybloodflowremained unchanged after reversal of arterial hypotension to a mean arterial pressure of 75 mmHg with norepinephrine. For the norepinephrine group versus the control group, the mean SD microcirculatory blood flow in the jejunum (96 41%vs.93 18%) and colon (98 19%vs.97 28%) and intestinal tissue oxygen tension (jejunum, 45 13 vs. 43 5 mmHg; colon, 50 10 vs. 45 8 mmHg) were comparable. Conclusions: In this model of abdominal surgery in which clinical conditions were imitated as close as possible, treatment of perioperative hypotension with norepinephrine had no adverse effects on microcirculatory blood flow or tissue oxygen tension in the intestinal tract.

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.

Abstract: Introduction The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups.

Inhibition of dopamine-β-oxidase by dietbyldithiocarbamate

Abstract: SIR,-Hydroxylation of dopamine to noradrenaline by dopamine8-oxidase has been postulated by Goldstein & Contrera (1961) as the rate-limiting step in the biosynthesis of noradrenaline. If this hypothesis is correct, then the tissue levels of noradrenaline should decrease when this enzyme is inhibited. However, Nikodijevic, Creveling & Udenfriend (I 963) using benzyloxyamine and benzylhydrazine analogues were unable to obtain significant decreases in the noradrenaline contents of guinea-pig tissues. More recently, Goldstein, Anagoste, Lauber & McKereghan (1964) found that diethyldithiocarbamate, a metabolite of disulphiram, was a potent inhibitor of dopamine8-oxidase. In the present work we have shown that diethyldithiocarbamate markedly reduced the noradrenaline levels and simultaneously increased those of dopamine in the small intestine of both the rat and rabbit.

SSRIs and SNRIs: A review of the Discontinuation Syndrome in Children and Adolescents.

Abstract: Objective To review the occurrence, clinical relevance and characteristics of the discontinuation syndrome in children and adolescents who have been on a selective serotonin reuptake inhibitor (SSRI) or a serotonin/norepinephrine re-uptake inhibitor (SNRI) for various conditions as an update for physicians prescribing these medications in this population.

Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

Abstract: In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hype...

Marked increases in plasma catecholamine concentrations precede hypotension and bradycardia caused by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious rats.

Abstract: Plasma noradrenaline and adrenaline responses to 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a selective putative 5-HT1A receptor agonist, have been studied in conscious, freely moving rats. Intravenously administered 8-OH-DPAT caused dose-related and sustained increases in plasma noradrenaline (2-fold) and adrenaline (11-fold) concentrations. Neither metergoline pretreatment (0.5 mg kg-1 i.v.) nor splanchnicectomy had any effect on the noradrenaline and adrenaline elevation caused by 8-OH-DPAT (250 micrograms kg-1 i.v.). The catecholamine responses peaked early but were still present during nadirs in blood pressure and heart rate. The discrepancy between plasma catecholamine and cardiovascular changes raises further questions about the mechanism of action of 8-OH-DPAT and supports other evidence suggesting a role for vagus stimulation in the cardiovascular effects caused by this drug.

Dose-dependent hemodynamic and metabolic effects of vasoactive medications in normotensive, anesthetized neonatal piglets.

Abstract: The developmentally regulated hemodynamic effects of vasoactive medications have not been well characterized. We used traditional and near-infrared spectroscopy monitoring technologies and investigated the changes in heart rate, blood pressure, common carotid artery (CCA) blood flow (BF), cerebral, renal, intestinal, and muscle regional tissue O2 saturation, and acid-base and electrolyte status in response to escalating doses of vasoactive medications in normotensive anesthetized neonatal piglets. We used regional tissue O2 saturation and CCA BF as surrogates of organ and systemic BF, respectively, and controlled minute ventilation and oxygenation. Low to medium doses of dopamine, epinephrine, dobutamine, and norepinephrine increased blood pressure and systemic and regional BF in a drug-specific manner, whereas milrinone exerted minimal effects. At higher doses, dopamine, epinephrine, and norepinephrine but not dobutamine decreased systemic, renal, intestinal, and muscle BF, while cerebral BF remained unchanged. Epinephrine induced significant increases in muscle BF and serum glucose and lactate concentrations. The findings reveal novel drug- and dose-specific differences in the hemodynamic response to escalating doses of vasoactive medications in the neonatal cardiovascular system and provide information for future clinical studies investigating the use of vasoactive medications for the treatment of neonatal cardiovascular compromise.

Treatment of cardiac conditions

Abstract: The invention relates to the treatment of cardiac dysfunction. In particular, certain compounds, believed to be glucagon-GLP-1 dual agonist compounds, exert a positive inotropic effect while preserving the energy balance of the heart, and so may be superior to known inotropic agents such as dobutamine, norepinephrine and glucagon.

Adrenergic Mediation of Hypoglycemia-Associated Autonomic Failure

Abstract: OBJECTIVE We tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans. RESEARCH DESIGN AND METHODS Seventeen healthy adults were studied on 2 consecutive days on three occasions. Day 1 involved hyperinsulinemic euglycemic (90 mg/dL × 1 h), then hypoglycemic (54 mg/dL × 2 h) clamps, in the morning and afternoon on all three occasions with 1 ) saline infusion, 2 ) adrenergic blockade with the nonselective α-adrenergic and β-adrenergic antagonists phentolamine and propranolol, or 3 ) adrenergic blockade plus cholinergic blockade with the muscarinic cholinergic antagonist atropine in random sequence. Day 2 involved similar morning euglycemic and hypoglycemic clamps, with saline infusion, on all three occasions. RESULTS Compared with the responses to hypoglycemia during saline infusion on day 1, the plasma epinephrine and norepinephrine responses to hypoglycemia were reduced on day 2 (351 ± 13 vs. 214 ± 22 pg/mL for epinephrine and 252 ± 4 vs. 226 ± 7 pg/mL for norepinephrine during the last hour; both P < 0.0001). However, the plasma epinephrine and norepinephrine responses to hypoglycemia were not reduced on day 2 when adrenergic or adrenergic plus cholinergic blockade was produced during hypoglycemia on day 1. CONCLUSIONS Adrenergic blockade prevents the effect of hypoglycemia to reduce the plasma catecholamine responses to subsequent hypoglycemia. Thus, adrenergic activation mediates the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans.

Isomeric octopamines: their occurrence and functions.

Abstract: p-Octopamine is a widely distributed invertebrate neurotransmitter (Evans 1978). It also occurs in the mammalian sympathetic nervous system, where its function is unknown (Axelrod & Saavedra 1977). Recent advances (Ibrahim et al 1984, 1985) in mass spectrometric analytical techniques have disclosed that, in addition to p-octopamine, 0and m-octopamine and the N-methyloctopamines (mand p-synephrine) also occur naturally in mammals. Evidence indicates that mand p-octopamine are located in sympathetic nerves with noradrenaline whereas mand p-synephrine are found only in adrenal gland (Ibrahim et al 1985). The location of o-octopamine is unknown but it is probably not in the same anatomical structure as mand p-octopamine and noradrenaline (Ibrahim & Williams 1985). This review summarizes the present knowledge concerning the distribution and possible functions of the three positionally isomeric octopamines.

Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycemia, and GLP-1 release in healthy older subjects

Abstract: Postprandial hypotension is an important problem, particularly in the elderly. The fall in blood pressure is dependent on small intestinal glucose delivery and, possibly, changes in splanchnic blood flow, the release of glucagon-like peptide-1 (GLP-1), and sympathetic nerve activity. We aimed to determine in healthy older subjects, the effects of variations in small intestinal glucose load on blood pressure, superior mesenteric artery flow, GLP-1, and noradrenaline. Twelve subjects (6 male, 6 female; ages 65-76 yr) were studied on four separate occasions, in double-blind, randomized order. On each day, subjects were intubated via an anesthetized nostril, with a nasoduodenal catheter, and received an intraduodenal infusion of either saline (0.9%) or glucose at a rate of 1, 2, or 3 kcal/min (G1, G2, G3, respectively), for 60 min (t = 0-60 min). Between t = 0 and 60 min, there were falls in systolic and diastolic blood pressure following G2 and G3 (P = 0.003 and P 1 kcal/min to elicit a significant fall in blood pressure, while the response may be maximal when the rate is 2 kcal/min. These observations have implications for the therapeutic strategies to manage postprandial hypotension by modulating gastric emptying.

Central Sympatholytic Drugs

Abstract: J Clin Hypertens (Greenwich). 2011;13:658–661. ©2011 Wiley Periodicals, Inc. Key Points • Central sympatholytic drugs reduce blood pressure mainly by stimulating central α2-adrenergic receptors in the brainstem centers, thereby reducing sympathetic nerve activity and neuronal release of norepinephrine to the heart and peripheral circulation. • This class of drugs, however, is currently used mainly as fourth-line (or beyond) drug therapy for hypertension because of side effects of drowsiness, fatigue, and dry mouth. • Rebound hypertension is also another major concern in certain drugs with a short half-life, particularly in patients who are nonadherent to the regimen. Therefore, their use on a “PRN” basis for treatment of blood pressure surge in the absence of symptoms or acute target complications should also be avoided.