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PubMed1982

Therapeutic trials of pindolol in hypertension: comparison and combination with other drugs.

The antihypertensive effect of pindolol has been demonstrated in several hundred clinical trials performed in many countries. The results of several representative trials will be reviewed in this article. In a cooperative study of pindolol by Swiss internists, blood pressure (BP) normalization was achieved in 76% of the patients and a fair response in 9%. In a French trial, BP reduction was found to correlate with the initial pressure level. Pindolol was also found effective in treating renal hypertension (Germany) and was considered particularly useful in hypertensive patients with coexistent angina pectoris (South Africa). A favorable effect on the BP profile registered during the whole day was demonstrated by means of BP telemetry (Germany). A Swedish long-term study showed pindolol to have a sustained antihypertensive effect over 16 months associated with a progressive decrease in systemic vascular resistance. In a study conducted in New Zealand, pindolol compared favorably with drugs previously used for hypertension, (methyldopa, diuretics, rauwolfia, guanethidine, etc.). It proved slightly less effective than methyldopa in a Canadian trial but significantly more effective than this drug in a South African study. Danish investigators found pindolol equivalent to chlorthalidone in lowering the resting BP but more effective than the diuretic in reducing the pressure and pulse response to exercise. Of particular interest are comparisons of pindolol with other beta-blockers performed in Germany, Sweden, Australia, and New Zealand. BP reductions obtained with pindolol did not differ significantly from those obtained with the other beta-blockers, whether they were cardioselective (metoprolol, atenolol) or not (propranolol, timolol, nadolol); however, pindolol produced less slowing of resting heart rate than these five other drugs, which are devoid of intrinsic sympathomimetic activity (ISA). Pindolol proved somewhat more effective than other nonselective beta-blockers with ISA (i.e., oxprenolol), although both produced less bradycardia than propranolol (New Zealand). In resistant cases, the combination of pindolol with diuretics, methyldopa, or hydralazine was found to significantly increase the responder rate.

Adrenergic beta-Antagonists↗
PubMed1982

Pulmonary function in hypertensive patients treated with pindolol: a report of two studies.

Pulmonary function was measured serially in two separate randomized trials of pindolol in the treatment of essential hypertension. Patients with overt obstructive airways disease were excluded. In study 1, 131 hypertensive patients were randomized to placebo (31) and 15 mg (33), 30 mg (33), and 60 mg (34) of pindolol. Pulmonary function was measured before and at weeks 8 and 15 of active medication. Bronchospasm--a 20% increase in forced expiratory volume in 1 second (FEV1) after isoprenaline--developed in three patients on active treatment and one on placebo. In eight patients on pindolol and one on placebo, bronchospasm ceased. Compared to placebo, no deterioration in pulmonary function occurred with pindolol and in three tests--maximum voluntary ventilation (MVV) (L/min), MVV%, midexpiratory flow rate (MEFR) (L/min)--significant improvement occurred. In study 2, 14 hypertensive patients were randomized to pindolol (mean dose 50 mg/day), 15 to propranolol (mean 360 mg/day), and 14 to chlorthalidone (mean 107 mg/day). Pulmonary function was measured after 3 weeks of placebo and again after 6 weeks of active treatment. While propranolol produced slight deterioration in pulmonary function, pindolol and chlorthalidone produced slight but significant improvement (p less than 0.05) with maximum MEFR (L/sec). Pulmonary function tests measured after isoprenaline were significantly worse in patients on propranolol compared to those on placebo, but were unchanged in patients on pindolol or chlorthalidone. The conclusions are: (1) Pindolol in antihypertensive doses does not produce airways obstruction and some improvement in pulmonary function may occur. (2) In comparable doses, pindolol has a positive effect on pulmonary function and propranolol a negative effect which, when summated, is statistically significant. (3) Propranolol, but not pindolol, appears to block the bronchodilator effects of isoprenaline. The lack of pulmonary function impairment may be due to intrinsic sympathomimetic activity properties of pindolol.

Chlorthalidone↗
PubMed1982

Pindolol postmyocardial infarction study: evaluation of the drug's antiarrhythmic and antianginal activity.

The study was designed to assess the antiarrhythmic and antianginal properties of pindolol as well as the tolerance to the drug by patients who had experienced a myocardial infarction 5 to 6 months previously. Exercise tests were performed in 521 postinfarct patients before and after a single oral 5 mg dose of pindolol. Depending on the physical condition of the patient, the initial work load was 25 or 50 watts, which was increased by 25 watts every 5 minutes. In patients with an initial heart rate (HR) of more than 68 bpm on the average, HR at rest was reduced with pindolol. This reduction was more pronounced the higher the initial HR. If the initial HR was below 68 bpm, HR increased slightly with pindolol, reflecting the drug's intrinsic activity. The frequency-regulating effect of pindolol dependent on the level of exercise that produced the tachycardia: tachycardia at rest responded more markedly to pindolol than exercise-induced tachycardia; tachycardia due to low-level exercise responded better than that due to higher level exercise. Of the 88 patients who developed typical effort angina and/or ischemic ST-segment depression, 62 became symptom free during exercise when taking pindolol. The patient sample included 66 patients with effort-related premature ventricular contractions (PVCs), 44 of whom responded well to pindolol. Of the 453 patients with a stable HR, 15 exhibited PVCs during exercise for the first time while receiving pindolol. Overall, pindolol exerted a statistically highly significant antiarrhythmic effect. Tolerance to pindolol was good; no side effects were observed.

Adult↗
PubMed1996

Effect of pindolol on the function of pre- and postsynaptic 5-HT1A receptors: in vivo microdialysis and electrophysiological studies in the rat brain.

In microdialysis studies, somatodendritic 5-HT1A receptors in the dorsal raphe nucleus (DRN) were activated by the local infusion of 50 microM citalopram, a selective 5-HT reuptake inhibitor (SSRI). This reduced extracellular 5-HT by about 50% in dorsal striatum, an area receiving 5-HT afferents exclusively from the DRN. (-)Pindolol dose-dependently attenuated this citalopram-induced reduction of striatal extracellular 5-HT. Consistent with its 5-HT reuptake blocking properties, single doses of the SSRI paroxetine (1 and 3 mg/kg IP) and citalopram (1 mg/kg IP) significantly elevated extracellular 5-HT in the dorsal striatum. Pretreatment with (-)pindolol (15 mg/kg IP) potentiated the effect of 3 mg/kg paroxetine and 1 mg/kg citalopram on striatal extracellular 5-HT. A 2-day treatment with 10 mg/kg/day (SC) of paroxetine reduced by 60% the spontaneous activity of 5-HT neurons of the DRN. However, 5-HT neurons displayed normal activity in rats treated with paroxetine and (-)pindolol for 2 days. The inhibitory effect of LSD on 5-HT neuronal firing activity was also markedly attenuated in (-)pindolol-treated rats, indicating that somatodendritic 5-HT1A receptors were blocked by (-)pindolol. To determine whether (-)pindolol also blocked postsynaptic 5-HT1A receptors in hippocampus, 5-HT and the prototypical 5-HT1A agonist 8-OH-DPAT were applied by microiontophoresis onto CA3 pyramidal neurons following the same treatment. (-)Pindolol did not modify the responsiveness of these neurons to 5-HT and 8-OH-DPAT. Taken together, these results indicate that (-)pindolol can potentiate the effects of an SSRI on extracellular 5-HT concentration by preventing the activation of somatodendritic 5-HT1A autoreceptors resulting from the blockade of the 5-HT transporter in the raphe. This presumably leads to enhanced 5-HT neurotransmission because (-)pindolol would not alter the responsiveness of certain postsynaptic 5-HT1A receptors, such as those located on hippocampal CA3 pyramidal neurons. These results provide a neurobiological basis for the reported potentiation of certain antidepressant drugs by pindolol in major depression.

Animals↗
PubMed2000

Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in humans: preliminary analyses.

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT(1A) receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT(1A) antagonist [carbonyl-(11)C]WAY-100635 or [carbonyl-(11)C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexa necarboxamide abbreviated as [(11)C]WAY-100635. Pindolol dose-dependently decreased [(11)C]WAY-100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/- 8% at scan 3, and 44 +/- 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT(1A) receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT(1A) receptors was higher in the DRN compared to cortical regions, demonstrating a significant in vivo selectivity for DRN 5-HT(1A) autoreceptors relative to cortico-limbic postsynaptic receptors. This selectivity is necessary for the potentiation of 5-HT transmission, and this finding represents an important proof of concept in the development of 5-HT(1A) agents for this application. Early evaluation of new drugs with PET imaging will enable rapid screening of compounds based on DRN selectivity and more appropriate determination of doses for clinical trials.

Adult↗
PubMed1992

Stereoselective inhibition of pindolol renal clearance by cimetidine in humans.

There are few data on whether differences exist in the renal tubular secretion of enantiomers and no data on whether inhibition of renal secretion of individual enantiomers is stereoselective. Pindolol was used as a probe drug because it is used clinically as a racemic mixture of R-(+) and S-(-) enantiomeric forms and is highly secreted by the proximal tubules of the kidney. Eight young healthy subjects received a single 15 mg oral dose of racemic pindolol with and without 400 mg cimetidine twice daily. The area under the plasma concentration-time curve of both R-(+)- and S-(-)-pindolol were significantly (p less than 0.01) increased by cimetidine from 234 +/- 90 (mean +/- SD) to 344 +/- 78 ng/ml.hr for R-(+)-pindolol and from 209 +/- 73 to 288 +/- 69 ng/ml.hr for S-(-)-pindolol. The renal clearance of R-(+)-pindolol (170 +/- 55 ml/min) was significantly (p less than 0.05) less than that for S-(-)-pindolol (222 +/- 66 ml/min). Cimetidine significantly (p less than 0.01) reduced the renal clearances of R-(+)-pindolol to 104 +/- 18 ml/min and for S-(-)-pindolol to 155 +/- 38 ml/min. The enantiomer with the higher renal clearance [S-(-)-pindolol] had its renal clearance reduced less by cimetidine (26% versus 34%, p less than 0.05). Cimetidine appears to have a stereoselective action on the active transport system for organic cations in the proximal tubule.

Administration, Oral↗
PubMed2000

Effects of sustained (+/-)pindolol administration on serotonin neurotransmission in rats.

OBJECTIVE: Given reports that (+/-)pindolol, a beta-adrenergic-5-HT1A/1B receptor antagonist, accelerates the onset of the therapeutic effect of certain antidepressant drugs in major depression, the aim of this study was to assess the effect of sustained (+/-)pindolol administration on the sensitivity of pre- and postsynaptic 5-HT1A receptors, terminal 5-HT1B autoreceptors and on overall 5-HT neurotransmission. DESIGN: Prospective animal study. ANIMALS: Sprague-Dawley rats. OUTCOME MEASURES: Modifications of the sensitivity of somatodendritic and postsynaptic 5-HT1A receptors using in vivo electrophysiological paradigms in animals treated with vehicle or (+/-)pindolol (20 mg/kg/day, subcutaneously) through osmotic minipumps for 2 weeks. RESULTS: (+/-)Pindolol attenuated the suppressant effect of the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons, suggesting that (+/-)pindolol antagonized somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. However, following a 2-day washout period, the suppressant effect of LSD was still attenuated, indicating rather a desensitization of 5-HT1A autoreceptors had occurred. In the CA3 region of the dorsal hippocampus, (+/-)pindolol treatment did not modify the responsiveness of postsynaptic 5-HT1A receptors to microiontophoretic applications of 5-HT. Moreover, such a treatment modified neither the effectiveness of the electrical stimulation of 5-HT fibers nor the function of terminal 5-HT autoreceptors. Finally, the administration of the selective 5-HT1A receptor antagonist WAY 100635 (100 micrograms/kg, intravenously) did not increase the firing activity of dorsal hippocampus CA3 pyramidal neurons in rats treated with (+/-)pindolol, thus failing to reveal the enhanced tonic activation of postsynaptic 5-HT1A receptors associated with major classes of antidepressant treatments. CONCLUSION: Prolonged administration of (+/-)pindolol by itself is not sufficient to enhance overall 5-HT neurotransmission; pindolol should therefore not be endowed with intrinsic antidepressant activity. Although pindolol is capable of antagonizing the 5-HT1A autoreceptor upon the initiation of a 5-HT reuptake-blocker treatment, it also induces a desensitization of this 5-HT1A autoreceptor, which could explain why patients do not relapse upon its discontinuation when they continue taking a 5-HT reuptake blocker.

Animals↗
PubMed2003

Milnacipran and pindolol: a randomized trial of reduction of antidepressant latency.

BACKGROUND: New, better tolerated and faster treatments for depression are needed. Patients are understandably unhappy with having to wait 3 to 4 weeks for a response to an antidepressant, while experiencing side effects almost immediately. This frequently has an adverse effect on compliance and engagement with treatment. AIMS: The primary objective was to assess the activity of pindolol on the onset of antidepressive response of milnacipran. The secondary objective was to assess the number of responders among the patients who received milnacipran and pindolol versus patients who received milnacipran and placebo. The tertiary objective was to evaluate the safety of milnacipran and pindolol versus milnacipran and placebo. METHOD: Randomized, double-blind, placebo-controlled study over 42 days. SETTING: Inner city London community mental health teams. PARTICIPANTS: 80 patients were selected and gave written consent to treatment, 78 were randomized (39 in each group) and evaluated for safety (intention-to-treat, ITT, safety data set), 77 (ITT efficacy data set), and 64 (per protocol, PP, data set) were evaluated for efficacy. The mean age was 31.9 for the pindolol group and 32.3 for the placebo. INTERVENTION: All patients received milnacipran 50 mg twice a day plus either pindolol 2.5 mg (the 'pindolol group') or matching placebo (the 'placebo group') three times a day. OUTCOME MEASURES: The main efficacy variable was the Montgomery-Asberg depression rating scale (MADRS) score at days 0, 4, 7, 10, 14, 21, 28, 42 on PP data set in an observation carried (OC) approach. Secondary efficacy variables were clinical global impression (global improvement) and Hamilton depression rating scale (HDRS). RESULTS: Improvement in MADRS total score was greater in the pindolol group than in the placebo group from day 7 (p=0.03). Responder rates in the clinical global impression were 97.2% for the pindolol group and 60.6% for the placebo group. The treatment was well tolerated with the most common side effects being nausea (28.2%; 35.9%), vomiting (7.7%; 23.1%), hot flushes (15.4%; 5.1%) and sweating (12.8%; 12.8%). CONCLUSION: The milnacipran and pindolol combination is safe, well tolerated and efficacious in major depression, and represents a rational strategy for the possible acceleration or potentiation of antidepressant action.

Adolescent↗
PubMed1982

Metabolism of pindolol in patients with renal failure.

Increased metabolism of pindolol in renal impairment has previously been suggested by pharmacokinetic calculations. The present study was a pharmacokinetic and metabolic investigation in 7 patients with severe renal impairment (endogeneous creatinine clearance below 5 ml/min). All the patients received pindolol 5 mg t.d.s. 5 days. On the sixth day, after an overnight fast, 14C-pindolol 5 mg was given orally as a solution to drink. Blood samples were taken for up to 72 h and urine was collected at intervals up to 96 h for measurement of unchanged pindolol by a fluorimetric method and total radioactivity by liquid scintillation counting. Metabolites in blood and urine were analysed after separation by HPLC. It was found that the plasma levels following a single dose of 14C-pindolol were similar to those observed in healthy volunteers, but the elimination half-life was slightly increased u tp 11.5 h. The observed steady state plasma concentrations of pindolol were twice as high but they are still in the therapeutic range of 10 to 100 ng/ml. Therefore, the dose of pindolol could have been reduced by a factor 2, but the reduction was not essential. No active metabolite of pindolol was found in plasma or urine, but elimination of the metabolites was decreased. The elimination half-life following multiple doses was prolonged compared to normal and it was quite comparable to that found fort pharmacodynamic half-life in renal patients. The discrepancy between the present findings and the previous results for metabolism and pharmacodynamic half-life was probably due to the sensitivity of the fluorimetric assay of pindolol.

Aged↗
PubMed1999

The use of pindolol with fluoxetine in the treatment of major depression: final results from a double-blind, placebo-controlled trial.

BACKGROUND: Preliminary reports have suggested that concomitant institution of pindolol and serotonin reuptake inhibitors robustly hastens clinical response; however, contradictory evidence from a randomized double-blind, controlled trial was recently reported by this group in a population of depressed patients who were prescribed fluoxetine and pindolol. Herein, we report final results from an extended sample size. METHODS: Drug-free outpatients with a major depressive episode were randomized in a double-blind manner to one of two treatment conditions: fluoxetine (20 mg daily) with pindolol (7.5 to 10 mg daily) or fluoxetine (20 mg daily) with placebo. After 6 weeks, patients were followed for 3 more weeks in a single-blind manner, on fluoxetine and placebo pindolol. RESULTS: Eighty-six patients completed at least 1 or more weeks on protocol, with 45 and 41 patients randomized to the pindolol and placebo groups respectively. After 2 weeks on protocol, partial remission (i.e., at least 50% decrease in depression rating scores from baseline) rates for pindolol (16%) and placebo (19%) groups were comparable. By the study's end, a partial remission was achieved, at least transiently, for 67% of the pindolol group and 80% of the placebo group. Pindolol treatment was associated with statistically significant reduction in blood pressure and pulse as compared to the control group. The two groups did not have overall differences in rates of attrition, time to response, and side effects. CONCLUSIONS: In accord with our previously published findings, these extended results do not support the efficacy of pindolol in hastening clinical response to fluoxetine in a patient population with predominantly chronic and recurrent depression.

Adult↗
PubMed1998

Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo.

1. It has been hypothesized that 5-HT1A autoreceptor antagonists may enhance the therapeutic efficacy of SSRIs and other antidepressants. Although early clinical trials with the beta-adrenoceptor/5-HT1 ligand, pindolol, were promising, the results of recent more extensive trials have been contradictory. Here we investigated the actions of pindolol at the 5-HT1A autoreceptor by measuring its effect on 5-HT neuronal activity and release in the anaesthetized rat. 2. Pindolol inhibited the electrical activity of 5-HT neurones in the dorsal raphe nucleus (DRN). This effect was observed in the majority of neurones tested (10/16), was dose-related (0.2-1.0 mg kg(-1), i.v.), and was reversed by the 5-HT1A receptor antagonist, WAY 100635 (0.1 mg kg(-1), i.v.), in 6/7 cases tested. 3. Pindolol also inhibited 5-HT neuronal activity when applied microiontophoretically into the DRN in 9/10 neurones tested. This effect of pindolol was current-dependent and blocked by co-application of WAY 100635 (3/3 neurones tested). 4. In microdialysis experiments. pindolol caused a dose-related (0.8 and 4 mg kg(-1), i.v.) fall in 5-HT levels in dialysates from the frontal cortex (under conditions where the perfusion medium contained 1 microM citalopram). In rats pretreated with WAY 100635 (0.1 mg kg(-1), i.v.), pindolol (4 mg kg(-1), i.v.) did not decrease, but rather increased 5-HT levels. 5. We conclude that, under the experimental conditions used in this study, pindolol displays agonist effects at the 5-HT1A autoreceptor. These data are relevant to previous and ongoing clinical trials of pindolol in depression which are based on the rationale that the drug is an effective 5-HT1A autoreceptor antagonist.

Action Potentials↗
PubMed1986

A double-blind comparison of indoramin and pindolol added to hydrochlorothiazide for the treatment of mild to moderate hypertension.

Sixty patients with mild to moderate essential hypertension, uncontrolled with diuretics alone, were evaluated in a double-blind randomized study that compared the effect of indoramin plus hydrochlorothiazide with that of pindolol plus hydrochlorothiazide. Following a 2-week period during which the patients were treated with 50 mg/day of hydrochlorothiazide, the patients were treated either with indoramin, 50-100 mg/day (n = 29), or with pindolol 10-20 mg/day (n = 30), in addition to the diuretic for 12 weeks. Systolic and diastolic blood pressures were significantly reduced after 2 weeks of treatment with indoramin or pindolol; blood pressure reduction was maintained for the 12 weeks of treatment. There were no significant differences between the indoramin and pindolol groups with respect to the changes in blood pressure. Blood pressure was controlled (less than or equal to 90 mm Hg) in 70% of the indoramin-treated patients and in 80% of the pindolol-treated patients. The difference was not significant. Heart rate was reduced after pindolol but not after indoramin. Side effects occurred in 20 patients (67%) treated with indoramin and in 14 patients (47%) treated with pindolol; the difference between the groups was not significant. Eight patients in the indoramin group and 10 patients in the pindolol group withdrew before completion of the study. In the indoramin group, four patients withdrew because of side effects and four because of lack of efficacy. In the pindolol group, five patients withdrew because of side effects and three because of lack of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pindolol increases plasma norepinephrine concentration by stimulation of beta 2-adrenoceptors in conscious spontaneously hypertensive rats.

The beta-adrenoceptor antagonist pindolol [10-1,000 micrograms/kg subcutaneously (s.c.)] caused dose-related decreases in mean arterial pressure (MAP) and increased heart rate (HR) in conscious spontaneously hypertensive rats (SHR). The lowest dose of pindolol (10 micrograms/kg) decreased MAP by 25 mm Hg (-16%) without affecting plasma norepinephrine (NE) or plasma renin concentration (PRC). However, higher doses of pindolol elicited dose-related increases in plasma NE concentration and PRC. Plasma epinephrine concentration was not altered by pindolol. The selective beta 2-adrenoceptor antagonist ICI 118,551 (3 mg/kg, s.c.) prevented the tachycardia but not the increase in PRC caused by 100 micrograms/kg pindolol. Treatment with ICI 118,551 completely eliminated the 45% increase in plasma NE elicited by 100 micrograms/kg of pindolol even though the decrease in MAP caused by this dose of pindolol was the same in the presence (-33 mm Hg) and absence (-34 mm Hg) of beta 2-adrenoceptor blockade. These results indicate that the vasodepressor action of pindolol in SHR does not result from an agonistic effect at postjunctional beta 2-adrenoceptors in the vasculature. In addition, the increases in plasma NE concentration produced by pindolol result from stimulation of beta 2-adrenoceptors. These beta 2-adrenoceptors may be located prejunctionally on sympathetic neurons.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

The relationship of plasma levels of pindolol in hypertensive patients to effects on blood pressure, plasma renin and plasma noradrenaline levels.

1. Fifteen, previously untreated, hypertensive patients were given 20 mg of pindolol, orally. The systolic and diastolic blood pressures fell significantly in 1 h; the effect was maximal 4 h after pindolol, and persisted for at least 8 h. 2. After oral administration of 20 mg of pindolol, its concentration in the plasma reached a peak in 2-3 h. At the end of 8 h, pindolol was not detectable in the plasma. 3. There was a significant relationship between the peak concentration of pindolol in plasma and the maximal change in blood pressure in fifteen previously untreated hypertensive patients. In a separate study of nine-nine hypertensive outpatients taking 15-80 mg of pindolol daily, the blood pressure responses corresponded generally to the concentration of pindolol in plasma 2-3 h after the morning dose. 4. There were no significant changes in plasma renin activity, plasma renin concentration or plasma noradrenaline concentration in the previously untreated patients taking 20 mg of pindolol. There was no relationship between initial plasma renin or noradrenaline levels and blood pressure responses to pindolol. Nor was there any significant relationship between the changes in plasma renin or noradrenaline levels and the changes in blood pressure.

Blood Pressure↗
PubMed1996

Pindolol and methylphenidate in children with attention-deficit hyperactivity disorder. Clinical efficacy and side-effects.

The purpose of this study was to examine the efficacy and side-effects of pindolol, a beta-blocker, in children with attention-deficit hyperactivity disorder (ADHD). Fifty-two ADHD children, 7-13 years old, participated in a prospective double-blind placebo-controlled comparison of pindolol and methylphenidate (MPH). Active treatment was pindolol and MPH: pindolol 20 mg b.i.d. or MPH 10 mg b.i.d. for 4 weeks. The outcome was assessed on the basis of the Abbreviated Conners Rating Scales (ACRS) completed by parents, teachers, and by a psychologist during psychological testing. Pindolol treatment was associated with a higher incidence of paraesthesias and with more intense nightmares and hallucinations than MPH or placebo treatment. These side-effects led to an interim change in design by ending pindolol treatment after 32 participants. Pindolol proved to be just as effective as MPH in decreasing hyperactivity and conduct problems at home, and hyperactivity problems at school. Pindolol, however, had less therapeutic effects than MPH during psychological testing, and failed to affect conduct problems in school. In sum, pindolol was modestly effective in the treatment of ADHD. Safety concerns on troubling side-effects clearly limit the use of it.

Adolescent↗
PubMed1986

The beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat.

The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. All the compounds studied caused a concentration-dependent increase in atrial frequency and relaxation of the uterus. The atrial response to pindolol was competitively inhibited by the beta 1-selective blocker pafenolol (10(-7) M), while the beta 2-selective blocker ICI 118551 (10(-8) M) was without effect. Pafenolol (10(-7) M) was also shown to inhibit the atrial frequency effect of alprenolol and oxprenolol. In the uterus, ICI 118551 (3 X 10(-9) M, 3 X 10(-8) M, 3 X 10(-7) M) blocked the pindolol effect with a pKB of 9.28. In addition, ICI 118551 (10(-8) M) competitively inhibited the relaxation of the uterus induced by alprenolol and oxprenolol. For alprenolol (right atrium and uterus), oxprenolol (right atrium), and pindolol (right atrium), the concentrations needed for half-maximal response were significantly greater than those required for occupation of half the receptors. This dissociation was most pronounced for pindolol in the right atrium. In this tissue, 80-85% of the beta 1-adrenoceptors had to be occupied by pindolol to initiate a tissue response corresponding to 50% of the maximal effect generated by the compound. The intrinsic activities of alprenolol, oxprenolol and pindolol (expressed as % of the maximal tissue response to isoprenaline) were significantly higher in the uterus than in the right atrium. The intrinsic activity of the compounds varied between individual preparations and, particularly in the uterus, correlated with the sensitivity of the tissue to beta-adrenoceptor stimulation by isoprenaline. 5 Calculation ofefficacy, relative to isoprenaline, of the partial beta-agonists revealed a beta 2-adrenoceptor selectivity for alprenolol (2.0), oxprenolol (1.4) and pindolol (3.0). 6 It is concluded that weak partial agonists such as alprenolol, oxprenolol and pindolol possess complex beta 1- and beta 2-adrenoceptor stimulatory properties in relation to beta-adrenoceptor occupancy and tissue sensitivity to beta-adrenoceptor stimulation.

Adrenergic beta-Agonists↗
PubMed1998

Effects of repeated clarithromycin administration on the pharmacokinetic properties of pindolol in rats.

The goal of the present work was to determine the effect of clarithromycin (CAM) administration on the pharmacokinetic properties of pindolol in rats. The binding of pindolol to serum components increases proportionally with increasing alpha1-acid glycoprotein (AGP) concentration, indicating that AGP might play a major role in the binding of pindolol. After intravenous administration of pindolol to rats, the CAM-treated group showed a decrease in the volume of distribution, an increase in AUC and no change in the half-life as compared to the control group. Treatment with CAM increased the AGP concentration only. The serum concentration of albumin and creatinine, as well as the metabolic activity of hepatic microsomes towards pindolol, were not altered. Good correlation was observed between the AUC of pindolol in rats and the AGP concentration in serum. Moreover, at 5 min after the administration of an intravenous bolus dose of pindolol to CAM-treated rats, the free concentration of pindolol was lower but the total concentration was higher, compared with the control rats. These results suggested that the influence of CAM on the pharmacokinetic properties of pindolol in CAM-treated rats can be explained by protein binding which, in turn, may be associated with variations in AGP concentration.

Adrenergic beta-Antagonists↗
PubMed1993

Mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries.

The mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries was studied. Single injections of pindolol (1-100 micrograms), propranolol (1-30 micrograms), and 5-hydroxytryptamine (5-HT, 0.001-1 microgram) produced a dose-related vasoconstriction in dog coronary arteries which were dilated by acetylcholine. l-Pindolol constricted coronary arteries, but d-pindolol did not. The responses to pindolol and propranolol were not affected by any of the following compounds (100 micrograms): bunazosin (a selective alpha 1-adrenergic antagonist), DG 5128 (a selective alpha 2-adrenergic antagonist), atropine (a muscarinic antagonist), chlorpheniramine (a selective H1-antagonist), cimetidine (a selective H2-antagonist), and ketanserin (a selective 5-HT2 antagonist). Methysergide (10 micrograms, a 5-HT1 and 5-HT2 antagonist) significantly reduced pindolol- and propranolol-induced vasoconstrictions, although it did not reduce norepinephrine-induced vasoconstriction in the presence of 5 microM propranolol. Methysergide (10 micrograms) and ketanserin (100 micrograms) significantly suppressed 5-HT-induced vasoconstriction. Diltiazem (100 micrograms, a calcium antagonist) and the incubation in Ca(2+)-free solution containing 1 mM EGTA for 1 hr significantly reduced the vasoconstrictions induced by pindolol and propranolol. The Ca(2+)-free solution containing 1 mM EGTA abolished the vasoconstriction induced by 5-HT in the presence of 1 microM ketanserine. In a solution containing 20 mM KCl, the vasoconstrictions caused by pindolol and propranolol were enhanced in dog coronary arteries. These results indicate that the direct contractile effects of pindolol on dog coronary arteries are mediated, at least partly, through 5-HT1-like receptors, but not through alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗