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At least 19 recordsLinked to original sources
PubMed1984

Antiarrhythmic action of bethanidine.

Studies were performed in 20 patients with symptomatic ventricular tachycardia (VT) to determine the efficacy of bethanidine compared with procainamide in preventing VT induced by programmed electrical stimulation. Before administering bethanidine, 5 to 10 mg/kg, the patients received 15 mg of protriptyline orally 24 and 2 hours before electrophysiologic studies to prevent the orthostatic hypotensive effects of bethanidine. Sustained VT (VT not spontaneously stopping) was induced in 8 and nonsustained VT (10 beats or more, terminating spontaneously) was induced in 4 patients. Bethanidine, 5 mg/kg, protected in 7 patients, and 10 mg/kg protected 1 additional patient. Procainamide, 1,000 and 1,500 mg intravenously, protected 8 of 16 patients. Bethanidine prevented VT induction in 50% of the patients not protected by procainamide. Bethanidine facilitated VT induction in 3 patients, while procainamide facilitated VT induction in 1 patient. Four patients with symptomatic VT have received bethanidine therapy for an average of 11 +/- 1.3 months, without clinical recurrence of their VT. Concomitant administration of protriptyline attenuated the acute hemodynamic changes caused by bethanidine and chronic combined therapy of protriptyline and bethanidine abolished the severe orthostatic changes in blood pressure caused by bethanidine. These studies show that bethanidine is effective in preventing VT induction and, thus, its use may not be restricted only to cases of primary ventricular fibrillation.

Bethanidine↗
PubMedDate not supplied

Electrophysiological effects of bethanidine sulfate on canine cardiac Purkinje fibers and ventricular muscle cells.

Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Purkinje fibers were exposed to bethanidine (10-80 mg/L) for 30-40 min. Bethanidine produced dose-dependent decreases in the maximal rate of depolarization (MRD) and over-shoot of phase 0, but did not affect maximum diastolic potential (MDP). Action potential plateau duration (APD, to -60 mV) was decreased by bethanidine at all cycle lengths of stimulation between 1,000 and 300 ms. Bethanidine depressed the membrane responsiveness curve, and its effects on MRD showed marked use dependence. In ventricular muscle cells, bethanidine 20 mg/L decreased MRD but did not affect MDP or APD. The rate of normal automaticity in Purkinje fibers with MDPs greater than -85 mV was increased to 21.5 +/- 5.6 beats/min after exposure to bethanidine (10 mg/L for 30 min) from control values of 10.2 +/- 5.3 beats/min. Abnormal automaticity (MDPs = -40 to -60 mV) was induced in Purkinje fibers by superfusion with Tyrode solution containing 0.25 mM BaCl2; this activity also was accelerated after exposure to bethanidine 10 mg/L. The effects of bethanidine on automaticity are similar to those of bretylium, and may be caused by release of endogenous catecholamines. In contrast, the effects of bethanidine on action potentials of normal (driven) Purkinje fibers are markedly different from those of bretylium, and resemble those of lidocaine after 30-60 min of exposure.

Action Potentials↗
PubMedDate not supplied

Bethanidine dose, plasma levels, and antihypertensive effects.

Bethanidine dose, plasma levels, and hypotensive effects were evaluated in twelve hypertensive patients. Diuretic therapy with benzthiazide was started two weeks before and continued during the study. Bethanidine was given three times daily. After two to 12 months of therapy in 11 of the patients, the mean standing diastolic pressure was reduced from 112 to 91 mm Hg. The mean total daily bethanidine dose was 79 mg (range 30--150 mg). The mean plasma bethanidine was 0.65 micrometer (range 0.1--2.8 micrometer), which correlated with the bethanidine dose. There was less correlation between dose and antihypertensive effect. The effects of sudden withdrawal from chronic bethanidine dosing were observed in six patients. The orthostatic effect of bethanidine was lost within 12 hours, but the half-time of elimination of bethanidine from plasma was 39 hours. Based upon the present findings, recommendations are presented for initiation and maintenance of antihypertensive therapy with bethanidine.

Adult↗
PubMed1988

The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart.

In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.

Animals↗
PubMed1982

Suppression of ventricular fibrillation and positive inotropic action of bethanidine sulfate, a chemical analog of bretylium tosylate that is well absorbed orally.

Bethanidine sulfate is a closely related chemical analog of bretylium that has virtually identical pharmacologic and antifibrillatory actions on the ventricle. Unlike bretylium, which is very poorly absorbed from the gut, bethanidine is rapidly and effectively absorbed after oral administration. Bethanidine increased ventricular fibrillation threshold in the normal dog heart from an average control value of 28.5 mA to an average peak value of 66.5 mA, an increase of 150 percent. In the infarcted heart, bethanidine increased ventricular fibrillation threshold from an average postinfarction level of 14.4 mA to an average peak value of 55.3 mA, an increase of 327 percent. Like bretylium, the antifibrillatory action of bethanidine was manifested by the appearance of nonsustained ventricular fibrillation when superthreshold shocks induced episodes of ventricular fibrillation lasting from 2 to 120 seconds and converting spontaneously to sinus rhythm. In contrast, the untreated dog heart must always be defibrillated electrically. The onset of antifibrillatory action began as early as 2 minutes after intravenous administration and 15 to 30 minutes after oral administration; peak action occurred in approximately 60 minutes. Bethanidine had prolonged positive inotropic action in the isolated heart as reflected by an increase in cardiac output and blood pressure lasting up to 60 minutes. Bethanidine lowered coronary vascular resistance and increased coronary blood flow. The oral efficacy and rapid onset of action gives bethanidine a potential role in the prevention of out-of-hospital ventricular fibrillation.

Administration, Oral↗
PubMed1984

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.

Adult↗
PubMed1989

Ischemia-induced conduction delay and ventricular arrhythmias: comparative electropharmacology of bethanidine sulfate and bretylium tosylate.

Bretylium tosylate and bethanidine sulfate were studied in two models of experimental myocardial ischemia. In anesthetized dogs, left anterior descending coronary artery occlusion during rapid atrial pacing (180-200 min-1) produced ventricular tachycardia and fibrillation within 5 min in 9 of 11 dogs studied. In all cases, arrhythmias were preceded by and appeared to be temporally related to progressive fractionation and delay of electrograms recorded from the ischemic zone. In four dogs, bretylium (10 mg/kg) did not alter the time course of electrogram changes nor the time to onset of arrhythmia. However, in five dogs bethanidine (10 mg/kg) markedly exacerbated conduction changes in the ischemic zone and decreased the time to onset of ventricular arrhythmias (173 +/- 35 vs. 262 +/- 34 s control, mean +/- SEM, p less than 0.05). Bethanidine administration also facilitated ischemia-induced ventricular tachycardia and fibrillation in two dogs that did not exhibit ischemia-induced arrhythmias before receiving the drug. In isolated perfused rabbit hearts, global ischemia produced conduction slowing, depolarization of resting membrane potential, and decreases in amplitude and Vmax that were reproducible in serial 10 min ischemic episodes. Bretylium (10 mg/L) did not affect these parameters under either perfused or ischemic conditions. Although bethanidine (10 mg/L) also did not affect these parameters during perfusion, conduction slowing and depression of Vmax during ischemia were accelerated without affecting the time course of change in resting membrane potential. Both bretylium and bethanidine prolonged action potential duration under perfused conditions, but after 10 min of ischemia this effect was no longer evident. The results demonstrate that differences in the electrophysiologic effects of bretylium and bethanidine are markedly accentuated in the setting of acute ischemia. Although both these agents have been demonstrated to have antifibrillatory effects in other experimental settings, under the conditions of this study, bretylium failed to protect against ischemia-induced arrhythmias and acute bethanidine administration produced a proarrhythmic effect in association with an exacerbation of ischemia-induced conduction changes.

Action Potentials↗
PubMed1988

Bethanidine increased Na+ and Ca2+ currents and caused a positive inotropic effect in heart cells.

The effects of bethanidine sulphate, a pharmacological analog of the cardiac antibrillatory drug, bretylium tosylate, were studied on action potentials (APs) and K+, Na+, and Ca2+ currents of single cultured embryonic chick heart cells using the whole-cell current clamp and voltage clamp technique. Extracellular application of bethanidine (3 X 10(-4) M) increased the overshoot and the duration of the APs and greatly decreased the outward K+ current (IK) and potentiated the inward fast Na+ currents (INa) and the inward slow calcium current (ICa). However, intracellular introduction of bethanidine (10(-4) M) blocked INa. In isolated atria of rat, bethanidine increased the force of contraction in a dose-dependent manner. These findings suggest that when applied extracellularly, bethanidine exerts a potentiating effect on the myocardial fast Na+ current and slow Ca2+ current and an inhibitory effect of IK. The positive inotropic effect of bethanidine could be due, at least in part, to an increase of Ca2+ influx via the slow Ca2+ channel and the Na-Ca exchange. It is suggested that the decrease of IK by bethanidine may account for its antifibrillatory action.

Action Potentials↗
PubMedDate not supplied

Bethanidine sulfate in paroxysmal ventricular tachycardia: toxicity and antifibrillatory actions.

Programmed ventricular stimulation was used to test oral bethanidine sulfate in 10 patients with life-threatening ventricular arrhythmias. These patients had previously documented, recurrent, sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) complicating stable heart disease. During control electrophysiologic studies, VT could be induced in all 10 patients: 6 with nonsustained VT, 3 with sustained VT, and 1 with VT/VF. After control, bethanidine 20-30 mg/kg was administered orally and beginning 60 minutes later, programmed ventricular stimulation was repeated. After bethanidine administration, VT could be induced in nine patients; in four, the VT was essentially unchanged from that induced during control studies. In four others, worse VT was induced after bethanidine. The remaining two patients had a potentially beneficial response to the drug. Bethanidine was poorly tolerated: seven patients had symptomatic orthostatic hypotension that persisted for several days despite concurrent protriptyline therapy. Furthermore, in four patients, spontaneous VT or VT/VF occurred 3-8 hours after the last dose. Nausea, vomiting, flushing, and blood pressure elevation were also noted. Bethanidine sulfate in the dosages used usually does not prevent the induction of VT by programmed ventricular stimulation and frequently causes serious toxicity. These findings suggest that the drug would be ineffective and poorly tolerated for long-term therapy in patients with serious ventricular arrhythmias.

Administration, Oral↗
PubMed1984

Acute electrophysiologic effects of bethanidine sulfate in patients with ventricular tachycardia or fibrillation.

Ten patients with a history of ventricular tachycardia or ventricular fibrillation underwent electrophysiologic study with programmed stimulation before and 90 minutes after oral administration of bethanidine sulfate, 20 mg/kg. Mean plasma bethanidine concentration was 2.62 +/- 2.2 (+/- SD) micrograms/ml at the start of repeat testing. This dose of bethanidine produced no effect on sinus node function, atrioventricular conduction, or atrial or ventricular refractoriness. Ventricular tachycardia or fibrillation, inducible in all patients during the control study, could still be initiated by ventricular stimulation in 9 of 10 patients after bethanidine. Bethanidine suppressed the ability to initiate an arrhythmia in one patient with ventricular fibrillation during control stimulation. Orthostatic hypotension was seen in all patients despite pretreatment with the tricyclic antidepressant, protriptyline, 15 mg every 8 hours. The results suggest that bethanidine has few electrophysiologic effects and is of limited efficacy during electrophysiologic testing in patients with life-threatening ventricular arrhythmias.

Aged↗
PubMed1982

Antiarrhythmic, antifibrillatory, and hemodynamic actions of bethanidine sulfate: an orally effective analog of bretylium for suppression of ventricular tachyarrhythmias.

Bethanidine sulfate is a chemical and pharmacologic analog of bretylium tosylate that has virtually identical antifibrillatory and inotropic actions on the heart. Bretylium is the only drug approved by the Food and Drug Administration specifically for the "prophylaxis and treatment of ventricular fibrillation." Unlike bretylium, which is poorly absorbed from the gut and limited to parenteral use, oral bethanidine is absorbed rapidly. Bethanidine was given to 23 patients with recurrent multiple drug refractory ventricular tachycardia and fibrillation. Eighteen patients (78%) had complete suppression of spontaneous or electrophysiologically inducible tachyarrhythmias; 3 were improved and 2 had no benefit. In 6 of a 9 patient subgroup studied by programmed electrophysiologic drug testing, bethanidine completely prevented previously inducible ventricular tachyarrhythmias at the maximal stimulus tested (including 4 extrastimuli and burst-pacing at 10 times threshold). Cardiac output measured in 6 patients 1 to 2 hours after bethanidine was increased in 4, unchanged in 2, and decreased in 1. Ten patients on long-term therapy with bethanidine and protriptylene (to prevent orthostatic hypotension) have been free of arrhythmias from 2 to 26 (average 13) months.

Adult↗
PubMedDate not supplied

Development of ventricular tachyarrhythmias in the conscious canine during the recovery phase of experimental ischemic injury: effect of bethanidine administration.

The antiarrhythmic and antifibrillatory actions of bethanidine were evaluated in two conscious canine models which are capable of developing ventricular tachyarrhythmias during the recovery phase of myocardial infarction. In the first model, nonsustained (n = 3) or sustained (n = 12) ventricular tachycardia (cycle length, 165 +/- 6 ms; mean +/- SD) was initiated by programmed electrical stimulation, 4-9 days after experimental myocardial infarction. Bethanidine was administered in cumulative doses of 2, 4, 8, and 16 mg/kg and programmed stimulation repeated. Bethanidine, in doses of 4, 8, and 16 mg/kg, slowed the cycle length of the tachycardia and allowed slower rates of ventricular pacing to produce equivalent delays at epicardial sites in the ischemic zone. Despite these changes, induction of sustained ventricular tachycardia was prevented in only two of 13 animals. Bethanidine (8 mg/kg i.v. every 8 h, n = 4; 16 mg/kg i.v. every 8 h, n = 5) failed to prevent the development of premature ventricular beats, ventricular tachycardia, and ventricular fibrillation which developed in response to a transient ischemic episode superimposed on the heart that had a previous acute myocardial infarction. No differences in survival at 24 h were observed between saline- (10%, n = 10) and bethanidine-treated (0%, n = 9) groups. These results suggest that bethanidine acts to increase the refractory period and depresses conduction velocity in ischemically injured tissue, slowing the rate of ventricular tachycardia. However, the drug fails to suppress the development of ventricular arrhythmias and ventricular fibrillation in both canine models.

Animals↗
PubMedDate not supplied

Studies on bethanidine and meobentine: direct and indirect effects of antifibrillatory drugs.

The electrophysiological effects of bethanidine and meobentine were studied on isolated canine cardiac tissues and the in situ dog heart using standard techniques. The "direct" electrophysiological effects of bethanidine (in the beta-adrenergic-blocked Purkinje fiber) resemble the effects of meobentine in the normal canine Purkinje fiber; both drugs produce use-dependent decreases of the maximum rate of depolarization of phase 0 and action potential amplitude. In addition, meobentine prolongs action potential duration (100%) of Purkinje fibers. In ventricular muscle cells, the only significant effect of meobentine is a decrease in the maximum rate of depolarization. In studies of ouabain-induced tachycardias and 24-h infarct-induced ventricular arrhythmias, bethanidine tends to increase heart rate and/or exacerbate the ectopic activity (due to its sympathomimetic effects), whereas meobentine tends to reduce heart rate and restore normal sinus rhythm. Both bethanidine and meobentine increase ventricular fibrillation threshold. This increase is evident following bethanidine injection after the subsidence of the sympathomimetic effects. Finally, moderate increases of ventricular fibrillation threshold following treatment with meobentine are accompanied by partial cardiac sympathetic blockade, as indicated by reduced chronotropic responses to stellate ganglion stimulation. The antiarrhythmic and antifibrillatory effects of bethanidine and meobentine may be explained by the use-dependent effects of these drugs on phase 0 of the action potential and by their sympatholytic actions on the autonomic nervous system. Meobentine may, in addition, exert antiarrhythmic effects by decreasing automaticity in partially depolarized cells.

Action Potentials↗
PubMed1977

Multiclinic controlled trial of bethanidine and guanethidine in severe hypertension.

One hundred and eight patients with initial diastolic blood pressure in the range of 100-124 mm Hg while taking hydrochlorothiazide were assigned randomly and double-blind to hydrochlorothiazide plus either bethanidine or guanethidine. The average reduction of the fifth and sixth months' diastolic blood pressure was 18.4 mm Hg for guanethidine and 13.6 mm Hg for bethanidine (P less than 0.01). The distribution of the individual values was such that 68.8% of guanethidine treated patients achieved a diastolic level below 90 mm Hg, compared to only 45.5% of the bethanidine treated group (P less than 0.025). The degree of orthostatic fall in blood pressure was greater with bethanidine than with guanethidine (P less than 0.05). The diurnal variation of blood pressure was slightly greater with bethanidine than with guanethidine. The results significantly favor guanethidine. This study failed to demonstrate that the shorter action of bethanidine confers significantly better control of blood pressure than the longer action of guanethidine.

Bethanidine↗
PubMed1975

Pharmacokinetics of bethanidine in hypertensive patients.

The pharmacolinetics of bethanidine-14C was studied in three hypertensive patients. A 25-MG DOSE OF BETHANIDINE-14 C hemisulfate was administered intravenously. Plasma levels of drug were measured over the first 6 hr. In 3 to 4 days, 89% to 94% of the dose was excreted in the urine. Thin-layer chromatography (TLC) and isotope dilution analysis of the urine samples indicated that only intact bethanidine was excreted. Plasma level and urinary excretion rate profiles had miltiphasic characteristics. Estimated half-lives of the terminal phase ranged from 7 to 11 hr. Average renal clearance over the initial 6 hr approached renal plasma flow. In 2 of the patients, renal clearance between 2 and 4 hr after administration was reduced to one-helf that observed during the initial 2-hr period. After single oral administration of a 25-mg dose of bethanidine-14C hemisulfate, 48% of 61% was excreted in urine and 15% to 48% in feces. Peak urinary excretion rates were reached 6 hr following administration. The urinary excretion kinetics of bethanidine during and after repetive oral dosing was also studied. A 25-mg dose was dividied into 12 to 16 equal doses and administered avery 6 hr. A larger fraction of the cumulative dose was recovered in the urine (72% to 74%) than after the single dose, suggesting higher availability at the lower dose. Steady-state urinary excretion rates were achieved in 4 to 7 doses. The steady-state urinary excretion levels were consistent with pharmacolinetic predictions based on single oral dose data. When 2 of the patients were given imipramine for 2 days prior to an oral 25-mg dose of bethanidine-14C hemisulfate, the terminal half-lives of the urinary excretion rate profiles were shorter than those in the same patients not given imipramine.

Administration, Oral↗
PubMed1975

The influence of topically applied bethanidine on intraocular pressure and pupil in the rabbit.

Bethanidine sulphate was administered topically to the eyes of conscious rabbits using a 0.5%, 1%, 2% and 5% solution of the drug. The intraocular pressures and pupil sizes were measured in the right treated and left control eyes at 0,1,2,3, 6 and 24 hrs. With all concentrations a pressure decrease with a maximum between 3 and 6 hrs after topical treatment occured. The 5% solution of bethanidine sulphate showed a delayed effect which was submaximal when compared to the 2% bethanidine solution. Using the 1% and 2% solution a ppressure decrease probably due to systemic action of the drug happened in the untreated control eyes. In all experiments the pressure responses had disappeared after 24 hrs in the treated and untreated eyes respectively. By means of the experimental conditions in this study no significant pupillary reactions were found after bethanidine application. The tension effect of 0.5% adrenaline borate remained essentially unchanged when repeated with additional 1% topical bethanidine. Some aspects of sympatholytic drug action on the intraocular pressure in the rabbit are discussed.

Animals↗
PubMed1985

Bethanidine sulfate: efficacy in prevention of ventricular tachyarrhythmias during programmed stimulation. Report of a multicenter study of 56 patients.

Twelve cardiac electrophysiology centers conducted an open label prospective trial of bethanidine sulfate, an oral bretylium analog, for the prevention of ventricular tachyarrhythmias during programmed electrical stimulation. The study group included 56 patients (44 men, 12 women; mean age 60 years; 55 with structural heart disease). Sixteen patients had both ventricular tachycardia and fibrillation, 30 had ventricular tachycardia alone and 10 had ventricular fibrillation alone. Programmed stimulation on no antiarrhythmic drugs induced sustained ventricular tachycardia in 46 patients, nonsustained ventricular tachycardia in 4 patients and ventricular fibrillation in 6 patients. During programmed ventricular stimulation after 59 trials of 20 to 30 mg/kg body weight of oral bethanidine (acute dosing in 40 patients, and divided dosing over 24 hours in 19 patients), no ventricular tachyarrhythmias were inducible in 6 patients (11%), sustained ventricular tachycardia was converted to nonsustained ventricular tachycardia in 3 patients (5%), ventricular tachyarrhythmias remained inducible in 39 patients (70%) and spontaneous ventricular tachyarrhythmias occurred more frequently in 4 patients (7%). Side effects prevented repeat testing in four patients. The 10 patients presenting with only ventricular fibrillation appeared to have a higher response rate: no ventricular tachyarrhythmias were inducible in 2 patients and sustained ventricular tachycardia was converted to nonsustained ventricular tachycardia in 2 patients. Despite protriptyline administration in 54 of 59 bethanidine trials, symptomatic hypotension occurred in 30 trials (51%). In conclusion, the efficacy of bethanidine for preventing ventricular tachyarrhythmias as assessed by programmed stimulation is low. Patients presenting with only ventricular fibrillation may have a more favorable response to bethanidine sulfate. Symptomatic hypotension occurs frequently despite concomitant use of protriptyline.

Adult↗
PubMed1977

Influence of desipramine on the uptake and efflux of radiolabelled bretylium and bethanidine in the adventitial and media-intimal layers of rabbit aortic strips.

The desipramine-sensitive uptake (neuronal uptake) of 14C-bretylium and 14C-bethanidine into the rabbit aortic adventitial layer from 3 X 10(-6) M solutions increased with time during a 20 min incubation. For both compounds a neuronal uptake of 50 pmol/50 mg wet weight adventitia was associated with 10% block of the contractile response to field stimulation at 16 Hz and 150 pmol/50 mg with 60% block. The concentration of blocking agents inside the neuron at 50% blockade was calculated to be 260 X 10(-6) M, an 87-fold increase over the medium. The bretylium in the neuron decreased by 50% during 20 min washout, and bethanidine by 29%. Desipramine when added to the bath 20 min following the addition of the blocking agents led to a loss of bretylium but not of bethanidine from the adventitia. Desipramine had little or no effect on the uptake, washout or disposition of either blocking agent in the media-intimal layers. The data indicate that bretylium has a greater propensity than bethanidine to be lost from the neurons; however, it appears to be recycled back through the membrane via the amine pump more readily than bethanidine. The fact that conservative calculations indicate that the neuronal membrane slowly established a concentration of the blocking agents within the neuron that is known to produce rapid local anesthesia when topically applied to adrenergic nerve trunks and which approaches a concentration needed to inhibit sensory endings suggests that local anesthesia may play a role in the mechanism of neuron blockade.

Animals↗