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PubMed1979

Presystemic and systemic glucuronidation of propranolol.

The relative importance of presystemic and systemic glucuronidation of propranolol was examined in normal subjects given single oral and intravenous doses of propranolol. The areas under the plasma concentration--time curves (AUCs) of propranolol glucuronide (PG), 41 +/- 15 ng . hr/ml, and propranolol, 48 +/- 15 ng . hr/ml, were of the same order after the intravenous dose (0.05 mg/kg). After oral doses of 20 and 80 mg, the AUCs of PG were 302 +/- 105 and 1,398 +/- 409 ng . hr/ml; these were 7 times the AUCs of propranolol, 44 +/- 15 and 220 +/- 38 ng . hr/ml. The time lapse to peak concentration, 1.5 to 3.0 hr, and the plasma half-life, 3.2 to 3.7 hr, were the same for PG and propranolol. These results demonstrate glucuronidation as an important determinant of propranolol bioavailability.

Administration, Oral↗
PubMed1979

Regional effects of propranolol on intraventricular conduction in coronary artery disease.

In canines, propranolol slows conduction in acutely ischemic, but not in normal tissues. To determine propranolol effects on conduction in patients with coronary artery disease, we studied 7 patients after left anterior descending coronary artery bypass graft surgery. Bipolar electrodes were placed in the atrium, left ventricle (in the left anterior descending distribution), and right ventricle. On postoperative day 7, 3 mg propranolol were given intravenously. At a constant artrially paced rate, conduction intervals were measured from the earliest onset of the QRS in 3 simultaneously recorded surface electrocardiogram (ECG) leads to the major deflection of the electrogram recorded from each ventricle. Ten minutes after injection, conduction in the left ventricle was slowed by 4 +/- 0.3 msec (10 +/- 0.9%) and in the right ventricle by 0.4 +/- 0.3 msec (1 +/- 0.9%). QRS duration changed -1 msec (-0.8%). Stimulus to Q, a measure of propranol effect on A-V conduction, changed 16 +/- 2%. The difference in propranolol effects on left and right ventricles was significant (p less than 0.001). We suggest that in patients with coronary artery disease (1) propranolol has local anesthetic effects in slowing conduction; (2) the effects of propranolol vary with the region of ventricular myocardium; and (3) propranolol slows conduction more in the left than right ventricle. This difference may be due to potentiation of drug effects in left ventricular tissue that is abnormal due to chronic coronary artery disease.

Adult↗
PubMedDate not supplied

Short-term effects of propranolol on portal venous pressure.

The present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 +/- 4.1 mm Hg. It decreased significantly 2 hr after the oral administration of 40 mg of propranolol to 15.7 +/- 4.2 mm Hg (a mean reduction of 13.4 +/- 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (greater than 20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of "responders" (those that reduced hepatic venous pressure gradient greater than 10%) and "nonresponders" (hepatic venous pressure gradient reduction less than 10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in the heart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction in hepatic venous pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The role of propranolol in congestive gastropathy of portal hypertension.

Heavy diffuse bleeding from congested gastric mucosa (congestive gastropathy) was treated by propranolol (dose = 24 to 480 mg per day) in 14 consecutive patients with portal hypertension. Thirteen patients (93%) stopped bleeding within 3 days. Gastric mucosal cherry red spots (a sign of severe gastropathy) were unchanged in 5 patients, became less obvious in 4 and appearances returned to normal in 5. Propranolol was discontinued electively in seven patients after 2 to 6 months; four of these patients rebled from the same lesion and stopped bleeding when propranolol was recommenced. No patient has rebled from congestive gastropathy while receiving propranolol during follow-up of 12 to 42 (median = 23) months. A further 24 patients with nonbleeding congestive gastropathy received 160 mg long-acting propranolol per day in a double-blind placebo controlled cross-over trial. Twenty-two patients completed the study; in nine patients, endoscopic grading of congestive gastropathy improved after propranolol compared to three after placebo (p less than 0.05). Although the mechanism of action is not understood, propranolol appears to have a clinically significant role in the management of nonvariceal gastric bleeding in portal hypertension.

Adult↗
PubMed1990

A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding.

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Effects of propranolol on gastric microcirculation and acid secretion in portal hypertensive rats.

Rats with chronic portal hypertension have an increased gastric mucosal blood flow and an impaired acid secretory response to pentagastrin stimulation. This study investigated the effects of propranolol, a drug widely used in the treatment of portal hypertension, on gastric mucosal blood flow and acid secretion in portal hypertensive rats with partial portal vein occlusion. In study I, gastric mucosal blood flow, measured by hydrogen gas clearance, and acid output were determined in basal conditions and after the administration of propranolol (0.3 mg/kg/min) or vehicle infusion in portal hypertensive and sham-operated rats. Gastric mucosal blood flow was significantly higher (p less than 0.005) in portal hypertensive rats than in sham-operated rats, and it was significantly reduced (p less than 0.05) after propranolol infusion in portal hypertensive rats (39 +/- 2 vs. 35 +/- 3 ml/min/100 gm). Basal acid output was not significantly modified with propranolol infusion, either in portal hypertensive or sham-operated animals. In study II, acid output was measured in portal hypertensive rats in basal conditions, during pentagastrin (20 micrograms/kg/hr) infusion and after the combined infusion of pentagastrin and propranolol (or vehicle). Pentagastrin infusion significantly increased (p less than 0.001) acid output, but propranolol did not modify stimulated gastric acid secretion. In conclusion, propranolol induced a slight but significant reduction in gastric mucosal blood flow and did not change basal or stimulated gastric acid secretion.

Animals↗
PubMed1993

Clearance by the liver in cirrhosis. II. Characterization of propranolol uptake with the multiple-indicator dilution technique.

We studied the steady-state hepatic extraction and single-pass hepatic uptake of propranolol in isolated perfused livers from normal rats and compared these values with those of rats with carbon tetrachloride-induced cirrhosis, rats treated with chlorpromazine (an inhibitor of propranolol metabolism) and rats with acute liver injury. The kinetics of propranolol transport in the liver were characterized by means of the multiple-indicator dilution technique, and estimates of cellular influx, efflux and sequestration rate constants were obtained with a computer fit to the model of Goresky. The outflow pattern of propranolol in the hepatic veins was then resolved into throughput material, which had swept past the hepatocytes along with albumin, and returning material, which had entered the cells but returned in the outflow after escaping metabolic sequestration. The steady-state extraction of propranolol was significantly decreased in the three experimental groups compared with that in controls, but the outflow profile differed within each group. In cirrhotic animals, influx was markedly decreased and the sequestration rate constant remained unchanged; most of the propranolol in the outflow consisted of throughput material. In rats treated with chlorpromazine, the sequestration rate constant was decreased, and propranolol in the outflow was mainly returning material. In rats with acute liver injury, both influx and sequestration rate constants were decreased. Indicator dilution curves for nonsequestered tracers showed a decreased transit time for red blood cells and abnormal diffusion of albumin and sucrose into the space of Disse in cirrhotic rats compared with the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Time couse of the blockade effect of propranolol on sinus node and atrioventricular node.

The time course of the blockade effect of propranolol on the sinus node (SN) and the atrioventricular node (AVN) was studied in six normal volunteers. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for two days. The inhibition by propranolol of the heart rate increases due to isoproterenol was used to assess the blockade of the sinus node, and the diminution by propranolol of the shortening in the PR interval due to isoproterenol was used to assess the blockade of the atrioventricular node. The blockade effects on the sinus node and the atrioventricular node were identical and persisted more than 24 hours. There was no good relationship between plasma propranolol and blockade effect on sinus node and/or atrioventricular node as propranolol was no longer detectable in the plasma 24 hours after the last dose. A transient hypersensitivity to isoproterenol was present 36 to 48 hours after propranolol withdrawal. The explanation of these phenomena most likely lies in the peculiar nature of beta-adrenergic receptors.

Adult↗
PubMed1988

Propranolol and inspiratory muscle performance in normal subjects.

We studied the effects of propranolol on respiratory muscle performance during inspiratory threshold-loaded endurance breathing in eight normal subjects. Propranolol (mean daily dose = 160 + 17 mg, SEM) reduced loaded 15-second MVV (92 versus 81 L/min;P = .01) and maximal sustainable ventilatory capacity (52.3 versus 44.5 L/min, P = .02) but did not affect the fraction of MVV, which was sustainable. Maximal static inspiratory pressures were reduced at two of three lung volumes, whereas maximal static expiratory pressures were unaffected by propranolol. The reduction in inspiratory muscle performance in the whole population could be accounted for almost entirely by four subjects who developed symptoms of "tiredness" and easy fatigability while receiving propranolol. There was no significant difference in propranolol dose, in degree of beta-receptor blockade, or in physical fitness in symptomatic and asymptomatic groups, and in neither group did propranolol alter pulmonary function test results. Propranolol directly depresses inspiratory muscle strength in subjects who develop drug-induced symptoms of fatigue by a mechanism probably unrelated to beta-adrenergic-receptor blockade.

Adult↗
PubMed1995

Pharmacokinetic and pharmacodynamic evaluation during coadministration of nefazodone and propranolol in healthy men.

Potential interactions between nefazodone (200 mg every 12 hours) and propranolol (40 mg every 12 hours) were assessed in 18 healthy male volunteers in an open-label, randomized, three-way crossover study. The nature, frequency, and severity of adverse events during coadministration of nefazodone and propranolol were similar to those observed with either treatment alone. There were no clinically significant effects on vital signs, electrocardiographic results, or laboratory parameters. With coadministration, the maximum peak concentration (Cmax) and area under the concentration-time curve over the dosing interval (AUC tau) of propranolol decreased 29% and 14%, respectively; Cmax and AUC tau of 4-hydroxy-propranolol decreased 15% and 21%, respectively. Despite decreased plasma concentrations of the beta-antagonists, the reduction in exercise-induced tachycardia and post-exercise double product was slightly greater with coadministration than with propranolol alone. Administration of nefazodone alone did not significantly affect either pharmacologic parameter. The pharmacokinetics of nefazodone and its metabolites were largely unaffected during coadministration. Coadministration of propranolol and nefazodone results in modest pharmacokinetic inequivalencies, but no clinically significant alterations of the pharmacodynamics of propranolol.

Adolescent↗
PubMed1991

Effects of propranolol on bone metabolism in the rat.

Propranolol, a nonspecific beta-blocker has many physiologic effects. Its effects on bone in vivo are unknown, although beta receptor sites have been found on osteoblasts. In this study, the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation. In a group of nonsurgical rats, propranolol treatment increased femoral torsional strength on biomechanical testing. In the rat surgical model used, right femora were fixed to a polyethylene plate and then defects were created mid-diaphysis and subsequently filled with demineralized bone matrix. These rats (defect rats) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days. In the defect rats, increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol-treated groups. Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol-treated rats revealed increased callus and bone union. The results of this study indicate that propranolol treatment can significantly affect bone properties.

Animals↗
PubMed2003

Disease-drug interaction: Reduced response to propranolol despite increased concentration in the rat with inflammation.

Inflammatory conditions reduce clearance, hence increase plasma concentration of drugs such as propranolol that are efficiently cleared by the liver. The therapeutic consequences of this increased plasma drug concentration is mainly unknown. However, for sotalol, another beta-adrenergic antagonist, inflammation causes reduced potency. Sotalol, however, is renally cleared; hence, its clearance is unaffected by inflammation. We examined if the inflammation-induced increased plasma propranolol concentration compensates for the reduced responsiveness. A modified lead I ECG was used to record PR interval and heart rate (HR). ECG was monitored following oral administration of 3, 5, 10, 15, 20, 25, and 30 mg/kg propranolol to both control and adjuvant arthritis (AA) rats. To confirm altered pharmacokinetics, single 25 mg/kg doses of propranolol were administered to both AA and control rats, with an inserted cannula in their right jugular vein for serial blood sampling. As expected, AA caused a significant reduction in the propranolol oral clearance and subsequently substantial increases in plasma total and unbound drug concentration. Interestingly, however, despite the elevated propranolol concentrations, the effect on HR remained unchanged and the prolongation of PR interval was significantly reduced in AA compared with control rats. The reduced sensitivity to propranolol in AA rats is suggestive of altered beta-adrenergic receptors function.

Adrenergic beta-Antagonists↗
PubMed1978

Fluorometric TLC determination of free and conjugated propranolol, naphthoxylactic acid, and p-hydroxypropranolol in human plasma and urine.

Sensitive, specific, and reproducible TLC methods are described for the determination of propranolol and its major metabolites in humans, conjugated propranolol, free and conjugated naphthoxylactic acid, and free and conjugated p-hydroxypropranolol. The drug or metabolites are extracted from plasma or urine with ether and applied to TLC plates of silica gel or microcrystalline cellulose. After development, the plates are scanned in a spectrodensitometer equipped to measure fluorescence in the UV and blue regions of the light spectrum. Quantitation is achieved by comparing the areas under the peaks obtained from the unknowns to those obtained from standards applied to the same plate. Limits of quantitation in plasma are: free propranolol, 2 ng/ml; free p-hydroxypropranolol, 10 ng/ml; conjugated propranolol, 15 ng/ml; total (free and conjugated) naphthoxylactic acid, 25 ng/ml; and conjugated p-hydroxypropranolol, 50 ng/ml. These methods were used to obtain plasma level data in a volunteer after one single dose of propranolol and in patients under propranolol therapy. The Rf values of some known metabolites of propranolol obtained in various TLC developing systems are also presented.

Chromatography, Thin Layer↗
PubMed1985

Effect of vitamin K3 on the first-pass elimination of propranolol in the rat.

The effect of vitamin K3, which inhibits electron transfer from NADPH to cytochrome P-450 via cytochrome c reductase, on the metabolism of propranolol was studied in the rat in vitro and in vivo. For in vitro experiments using rat liver microsomes, the metabolism of propranolol was inhibited by vitamin K3. For in vivo experiments, the area under the blood concentration-time curve and the maximum concentration of propranolol were markedly increased following intraportal infusion of propranolol with vitamin K3, but intraportal administration of vitamin K3 had little effect on propranolol kinetics when propranolol was infused intravenously. Thus, it was concluded that vitamin K3 inhibited the first-pass metabolism of propranolol.

Animals↗
PubMed2001

Structural basis for enantiomer binding and separation of a common beta-blocker: crystal structure of cellobiohydrolase Cel7A with bound (S)-propranolol at 1.9 A resolution.

Cellobiohydrolase Cel7A (previously called CBH 1), the major cellulase produced by the mould fungus Trichoderma reesei, has been successfully exploited as a chiral selector for separation of stereo-isomers of some important pharmaceutical compounds, e.g. adrenergic beta-blockers. Previous investigations, including experiments with catalytically deficient mutants of Cel7A, point unanimously to the active site as being responsible for discrimination of enantiomers. In this work the structural basis for enantioselectivity of basic drugs by Cel7A has been studied by X-ray crystallography. The catalytic domain of Cel7A was co-crystallised with the (S)-enantiomer of a common beta-blocker, propranolol, at pH 7, and the structure of the complex was determined and refined at 1. 9 A resolution. Indeed, (S)-propranolol binds at the active site, in glucosyl-binding subsites -1/+1. The catalytic residues Glu212 and Glu217 make tight salt links with the secondary amino group of (S)-propranolol. The oxygen atom attached to the chiral centre of (S)-propranolol forms hydrogen bonds to the nucleophile Glu212 O(epsilon1) and to Gln175 N(epsilon2), whereas the aromatic naphthyl moiety stacks with the indole ring of Trp376 in site +1. The bidentate charge interaction with the catalytic glutamate residues is apparently crucial, since no enantioselectivity has been obtained with the catalytically deficient mutants E212Q and E217Q. Activity inhibition experiments with wild-type Cel7A were performed in conditions close to those used for crystallisation. Competitive inhibition constants for (R)- and (S)-propranolol were determined at 220 microM and 44 microM, respectively, corresponding to binding free energies of 20 kJ/mol and 24 kJ/mol, respectively. The K(i) value for (R)-propranolol was 57-fold lower than the highest concentration, 12.5 mM, used in co-crystallisation experiments. Still several attempts to obtain a complex with the (R)-enantiomer have failed. By using cellobiose as a selective competing ligand, the retention of the enantiomers of propranolol on the chiral stationary phase (CSP) based on Cel7A mutant D214N were resolved into enantioselective and non- selective binding. The enantioselective binding was weaker for both enantiomers on D214N-CSP than on wild-type-CSP.

Adrenergic beta-Antagonists↗
PubMed1997

Chronic treatment with propranolol induces antioxidant changes and protects against ischemia-reperfusion injury.

The goal of this study was to examine whether chronic administration of propranolol offers protection against ischemia-reperfusion injury and whether it induces any change in the myocardial endogenous antioxidant enzyme activities and their gene expression. Rats were treated with propranolol (10 mg/kg/day, i.p.) for either 6 or 18 days. Forty-eight h after the last propranolol injection, isolated hearts were subjected to 60 min of global ischemia and 40 min of reperfusion. Resting tension in the control and treated groups after ischemia was 385+/-30 and 150+/-15%; and upon reperfusion was 140+/-11 and 49+/-6%, respectively, as compared to the pre-ischemic values. Recovery of the contractile function in globally ischemic hearts upon reperfusion was about 35% in the treated group as compared to about 16% in the control group at 10 and 20 min. A positive response to catecholamine was observed in hearts from propranolol group (C, 3.41+/-0.36; epi, 6.03+/-0.47 g/g) and was comparable to control hearts (C, 3.55+/-0.31; epi, 6.48+/-0.42 g/g). Myocardial antioxidants, catalase and glutathione peroxidase enzyme activities, in the treated group, prior to ischemia-reperfusion were increased by 67+/-9 and 45+/-11%, respectively, over those in controls. Superoxide dismutase activity did not show any change. The mRNA expression for the three antioxidant enzymes did not change in the hearts of the treated group as compared to control. Lipid peroxidation, both before and after the ischemia-reperfusion episode, was significantly reduced in the propranolol-treated hearts compared to the control group. Hearts studied at the end of reperfusion showed no difference in enzyme activities between treated and control groups. These data show that propranolol treatment of the animals protects against ischemia-reperfusion injury in isolated hearts in the absence of beta-blockade. Increased endogenous antioxidant enzyme activities due to propranolol treatment may have a role in this protection.

Adrenergic beta-Antagonists↗
PubMed1994

Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise.

The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers. At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (-27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (-7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (-20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h). After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine. We conclude that the beta 2-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the beta-adrenoceptor blockade-induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the beta-adrenoceptor antagonist activity of dilevalol was apparent.

Adult↗
PubMedDate not supplied

Propranolol inhibits nonexocytotic noradrenaline release in myocardial ischemia.

Ischemic induces a nonexocytotic noradrenaline release in the heart, which leads to high and potentially harmful interstitial noradrenaline concentrations. The effect of beta-adrenoceptor antagonists on noradrenaline release in ischemia has been investigated in the present study. DL-Propranolol (1-100 mumol/l) concentration-dependently reduced noradrenaline release during 20 min of global and total ischemia in the perfused rat heart. Other beta-adrenoceptor blocking agents such as atenolol, metoprolol, and timolol (10 mumol/l each), however, did not share this effect. Moreover, both stereoisomers of propranolol were equipotent in suppression of ischemia-induced noradrenaline release, indicating a property of propranolol independent from interaction with beta-adrenoceptors. The well known local anesthetic action of propranolol was not likely to cause its inhibitory effect on ischemia-induced noradrenaline release, as lidocaine (10 mumol/l) did not affect noradrenaline overflow in ischemia. The effect of propranolol was further examined in cyanide intoxication, an experimental model of energy depletion. In this experimental setting the release of dihydroxyphenylethyleneglycol--the major neuronal metabolite of noradrenaline--served as indicator of increased axoplasmic noradrenaline levels which are present during nonexocytotic noradrenaline release. In cyanide intoxication DL-propranolol also reduced noradrenaline overflow but did not affect release of dihydroxyphenylethylene glycol. The latter finding suggests an interaction of propranolol with the neuronal membrane transport of noradrenaline. In ischemia and cyanide intoxication, transport of noradrenaline across the plasma membrane is known to be driven by the noradrenaline carrier (uptake1) working in reverse of its normal direction--from inside to outside. Consequently, inhibitors of the noradrenaline carrier like desipramine were shown to suppress nonexocytotic noradrenaline release in ischemia and cyanide intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗