Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pindolol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2000

Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5-HT1A receptors.

Pindolol accelerates the clinical actions of selective serotonin reuptake inhibitors (SSRIs) in man, and modulates extracellular levels of monoamines in corticolimbic structures in rats. Herein, we examined its influence upon electrical activity of serotonergic, dopaminergic and adrenergic perikarya in the dorsal raphe nucleus (DRN), ventral tegmental area (VTA) and locus coeruleus (LC) of anaesthetized rats. In analogy to the serotonin1A (5-HT1A) agonist, 8-OH-DPAT (-100%), pindolol dose-dependently (0.063- 1.0 mg/kg) decreased (-70%) the firing rate of serotonergic neurons. The inhibitory action of pindolol was abolished by the selective 5-HT1A antagonist, WAY-100,635 (0.031 mg/kg). In contrast, 8-OH-DPAT (+26%) and pindolol (0.25-4.0 mg/kg, +60%) dose-dependently increased the firing rate of dopaminergic cells. Of 57 neurons recorded (pindolol, 2.0 mg/kg), 36 (63%) were excited, 11 (19%) were unaffected and 10 (18%) were inhibited. This variable influence could be attributed to regularly firing neurons in the parabrachial subdivision, inasmuch as all neurons in the paranigral subnucleus were excited. The facilitation of firing by pindolol was accompanied by an increase in burst firing throughout the VTA. Both the increases in burst firing and in firing rate were reversed by WAY-100,635 (0.031 mg/kg). Finally, the electrical activity of adrenergic neurons was dose-dependently enhanced by 8-OH-DPAT and pindolol (+99% and +83%, respectively). WAY-100,635 reversed this excitation and, itself, inhibited the activity of adrenergic neurons. In conclusion, via engagement of 5-HT1A receptors, pindolol inhibits serotonergic, and activates dopaminergic and adrenergic, neurons in anaesthetized rats. Such actions may contribute to its influence upon mood, both alone and in association with antidepressant agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Does the addition of pindolol accelerate the response to electroconvulsive therapy in patients with major depression? A double-blind, placebo-controlled pilot study.

There is evidence that addition of pindolol, a beta-adrenergic/5-hydroxytryptamine-1A antagonist, can accelerate the onset of action of antidepressant medications. The purpose of this study was to determine whether pindolol administration can induce a rapid improvement in depressive symptoms in patients receiving electroconvulsive therapy (ECT) within six ECT treatments. A total of 20 patients with DSM-IV-diagnosed major depression who were undergoing a course of ECT as the clinically indicated treatment were recruited. They were neuroleptic, lithium, and antidepressant free for at least 1 week before the study. Of the 20 patients, 9 patients had been randomly assigned to receive pindolol 2.5 mg three times daily, and 11 patients received identical placebo three times daily for the duration of the first 6 ECT treatments. One of 9 patients in the pindolol group and 4 of 11 patients in the placebo group dropped out of the study. Using an outcome measure of a score < or =12 on the 29-item Hamilton Rating Scale for Depression (HAM-D), the authors found that four (50%) of eight patients responded to the combination treatment of ECT and pindolol within six ECT treatments. In contrast, none (0%) of seven patients who received placebo responded to ECT treatment. Furthermore, both mean 29-item HAM-D and Clinical Global Impression Scale scores after the sixth ECT treatment were significantly lower in patients treated with pindolol compared with those treated with placebo. However, the number of total ECT treatments within a course or the overall efficacy of ECT treatment was not altered by the addition of pindolol. The results of this study suggest that within six ECT treatments, pindolol administration hastens antidepressant effects of ECT in some depressed patients.

Adrenergic beta-Antagonists↗
PubMed1982

Haemodynamic effects of metoprolol and pindolol: a comparison in hypertensive patients.

1 In a double-blind study, 36 patients with essential hypertension were randomly allocated to treatment with either metoprolol, 100--300 mg/day, or pindolol, 5--15 mg/day for 6 months. Haemodynamic investigations were made on three separate occasions. Blood flow in the calves and in the forearm was determined by venous occlusion plethysmography after 6 weeks of placebo, after 6 weeks and again after 6 months of active therapy. 2 Both drugs reduced blood pressure significantly, by 17.1/11.8 mm Hg with metoprolol and 21.9/10.9 mm Hg with pindolol after 6 weeks (P less than 0.005). No further changes were seen after 6 months. 3 Heart rate after 6 weeks was significantly reduced by metoprolol (10.7 +/- 2.4 beats/min, P less than 0.001) but not by pindolol (4.4 +/- 2.3 beats/min, NS). After 6 months a significant reduction was seen also in the pindolol group (5.2 +/- 2.1 beats/min, P less than 0.05). 4 The vascular resistance in the calves at rest was reduced by pindolol (P less than 0.05), whereas resistance tended to increase with metoprolol. 5 Resting vascular resistance in the forearm after 6 months was significantly reduced in the metoprolol group (P less than 0.001) as well as in the pindolol group (P less than 0.02). The increase in forearm vascular resistance seen during leg exercise was not influenced by either drug. 6 Vascular resistance at maximal vasodilatation was unchanged in the calves, but a significant reduction (-17.4 +/- 5.7%, P less than 0.01) in the forearm vascular bed was seen after 6 months of pindolol. No change was observed with metoprolol. 7 It is concluded that pindolol reduces elevated blood pressure partly through peripheral vascular mechanism. Metoprolol, on the other hand, probably acts mainly via central cardiac mechanisms.

Adult↗
PubMed1999

Inhibition of lipid peroxidation by pindolol.

Among beta-blockers, including atenolol, metaproterenol, pindolol and propranolol, only pindolol strongly inhibited lipid peroxidation induced by xanthine oxidase-hypoxanthine in the presence of adenosine-5'-phosphate-Fe3+. In the reaction system, superoxide predominantly reduced iron because superoxide dismutase strongly prevented the iron reduction. However, pindolol had no effect on the superoxide-dependent iron reduction. Adding superoxide dismutase immediately stopped the lipid peroxidation, indicating that superoxide is closely connected with forming the initiator of xanthine oxidase-hypoxanthine-induced lipid peroxidation. On the other hand, pindolol also inhibited lipid peroxidation, whereas it did not react with superoxide, indicating that it inhibited xanthine oxidase-hypoxanthine-induced lipid peroxidation by an independent mechanism of superoxide. Pindolol sharply scavenged 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) radical cations, but the ability of pindolol to scavenge peroxyl radicals of 2,2'-azobis(2-amidinopropane)-dihydrochloride and 2,2'-diphenyl-p-picrylhydrazyl radicals was low. In addition, pindolol did not scavenge hydroxyl radicals at physiologically significant concentrations. These results suggest that the ability of pindolol to inhibit lipid peroxidation was due to scavenging carbon-centered radicals rather than peroxyl radicals.

Adenosine Diphosphate↗
PubMed2006

Pindolol augmentation of antidepressant response.

Pindolol, a partial beta-adrenoceptor/5-HT1A receptor antagonist was first used to accelerate the onset of action of antidepressant drugs in 1994. Since then, it has been used in more than a dozen controlled trials to examine whether it can reduce the lag to clinical improvement, and/or improve the clinical response in treatment-resistant patients. A recent metaanalysis concluded that pindolol accelerates the antidepressant response but does not increase the effectiveness of SSRIs in unresponsive patients. Several studies have examined the pharmacology of pindolol to clarify the neurobiological basis of its clinical action. Pindolol was initially used due to its ability to block 5-HT1A receptor-mediated responses and to enhance the neurochemical effects of SSRIs. In transfected cells, however, pindolol is a weak (20-25%) partial agonist at 5-HT1A receptors and, as such, its actions greatly depend on the system used. In line with this, other reports have also shown that pindolol can reduce serotonergic cell firing when given alone. Positron emission tomography (PET) scan studies have shown that pindolol displays a preferential occupancy of pre- vs. postsynaptic 5-HT1A receptors, although the overall occupancy is lower than desirable, which suggests that higher doses (e.g., 15 mg/day) may be more effective than the currently used 7.5 mg daily dosage. However, given the complex pharmacology of pindolol, it is hoped that new developments in this field can proceed through the use of a) selective and silent 5-HT1A receptor antagonists in combination with SSRIs, or b) dual action agents (SSRI+5-HT1A receptor blockers).

Brain↗
PubMed1976

[Comparative study on the elimination of pindolol (visken) and antipyrin in patients with liver diseases].

25 patients suffering from different hepatic diseases were studied in order to investigate the elimination of the beta-receptor blocking drug pindolol in hepatic disease. Following an overnight fasting period the patients received simultaneously 3 mg pindolol intravenously and 1000 mg antipyrine orally. Plasma samples were taken at certain time intervals for 24 hs and urine was collected for 72 hs for the measurements of drug concentrations in plasma and urine. From these measurements different pharmacokinetic parameters were calculated for both drugs used in the present study according to a one-compartment open model. The total body clearance of antipyrine was selected as a parameter of the metabolic capacity of the liver microsomal enzyme system and was compared with the pharmacokinetic parameters calculated for pindolol by means of linear regression. There was no significant correlation between the total body clearance of antipyrine and the kinetic parameters of pindolol in any of the 25 patients irrespective of the differences in liver disease. On the other hand, 14 patients suffering from cirrhosis of the liver showed a significant correlation between the total body clearance of antipyrine and the overall elimination rate constant or metabolic clearance of pindolol. No correlation was found between antipyrine clearance and total body clearance of pindolol, as some patients with intact renal function excreted a higher proportion of pindolol in the urine as liver function decompensated. The mechanism of such compensatory elimination is unknown. In conclusion, the total body clearance of antipyrine known to represent metabolic liver function showed a significant correlation with the metabolic clearance of pindolol in patients with cirrhosis of the liver. For the other liver diseases investigated, too few patients were studied to calculate an adequate correlation.

Antipyrine↗
PubMed1999

Pindolol, a putative 5-hydroxytryptamine(1A) antagonist, does not reverse the inhibition of serotonergic neuronal activity induced by fluoxetine in awake cats: comparison to WAY-100635.

The ability of pindolol to enhance the clinical antidepressant response to selective serotonin reuptake inhibitors (SSRIs) is generally attributed to a blockade of the feedback inhibition of serotonergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to restore the single-unit activity of serotonergic dorsal raphe nucleus neurons in awake cats after acute treatment with the SSRI fluoxetine. The effects of pindolol were compared with those of N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY-100635), a selective 5-HT(1A) receptor antagonist. Systemic administration of fluoxetine (0.5 and 5 mg/kg i. v.) decreased neuronal firing rates to approximately 50 and 1%, respectively, of baseline levels. The subsequent administration of cumulative doses of (+/-)-pindolol (0.1-5 mg/kg i.v.) failed to reverse the neuronal inhibition produced by either dose of fluoxetine. In addition to lacking efficacy as an antagonist in these experiments, (+/-)-pindolol produced an additional decrease in neuronal activity in animals pretreated with the low dose of fluoxetine. The active enantiomer, (-)-pindolol (1 mg/kg i.v.), also was ineffective in restoring neuronal activity after fluoxetine. In contrast, systemic administration of WAY-100635 completely reversed the effect of fluoxetine (5 mg/kg) at low doses (0.025 mg/kg i.v.), and further elevated the firing rate of these neurons above prefluoxetine baseline levels. Overall, these results indicate that pindolol, unlike WAY-100635, lacks appreciable antagonist activity at 5-HT(1A) autoreceptors. Thus, the clinical efficacy of pindolol in augmenting the antidepressant response to SSRIs, such as fluoxetine, may be unrelated to a restoration of serotonergic neuronal activity.

Animals↗
PubMed1982

Adverse reactions to pindolol administration.

More than 1200 patients who received pindolol for the treatment of hypertension, angina pectoris, and various arrhythmias in studies conducted in the United States were included in the New Drug Application submitted to the FDA. Nearly 1000 of these patients received pindolol as monotherapy. The side effects reported were generally transient and of mild or moderate severity. The most frequently reported side effects seen after pindolol administration, compared to those seen after placebo, were in decreasing order of incidence: headache, dizziness, insomnia, muscle pain, fatigue, weakness, nervousness, joint pain, edema, nausea, and muscle cramps. Other side effects that occurred more frequently with pindolol than with placebo but at a rather low incidence induced weight gain, bizarre dreams, visual disturbances, lethargy, and diarrhea. Nasal congestion, throat discomfort, nocturia, impotence, pruritus, anxiety, hypotension, bradycardia, and heart failure occurred only rarely. Of the 323 patients who received pindolol alone for the treatment of mild to moderate hypertension, only 20 (6.2%) were withdrawn from the study because of side effects. Overall, 3.4% of the patients treated with pindolol were withdrawn because of side effects, most of which involved the central nervous system, that is, insomnia, anxiety, dizziness, and headache. However, a few patients manifested some edema and weight gain while receiving pindolol alone. Review of the side effects data did not reveal a tendency for the incidence of side effects to be dose related. One placebo-controlled, double-blind study designed to evaluate the fixed dosages of 15, 30, and 60 mg in the treatment of mild to moderate hypertension suggested that only the incidences of insomnia and nervousness increased with increasing doses. However, these side effects were generally transient and of mild or moderate severity. The evidence indicates that pindolol has an acceptable safety profile and that any side effects that appear are generally well tolerated and disappear with continued treatment.

Chlorthalidone↗
PubMed1999

A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en Trastorns Afectius.

BACKGROUND: Pindolol has been reported to hasten the antidepressant action of selective serotonin reuptake inhibitors in open-label and placebo-controlled trials. Pilot studies also suggested that pindolol could augment the antidepressant response in unresponsive patients. We investigated whether the addition of pindolol can induce a rapid response in treatment-resistant patients. METHODS: After a single-blind lead-in placebo phase of 5 days to exclude placebo responders, 80 outpatients with major depression who did not respond to a minimum of 6 weeks of treatment with clomipramine hydrochloride, 150 mg/d; fluoxetine hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or paroxetine hydrochloride, 40 mg/d, were randomly assigned to additionally receive placebo (3 times daily) or pindolol (2.5 mg 3 times daily) for 10 days. The median number of ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating Scale for Depression and Montgomery-Asberg Scale for Depression scores were used as primary measures of efficacy. RESULTS: At end point, the Hamilton and Montgomery-Asberg scores and change from baseline in Hamilton score were not significantly different in patients taking placebo or pindolol. The response rate was equal in both groups (12.5%). No differences in the clinical outcome were found when the various pretreatment subgroups were considered. At end point, the plasma concentration of pindolol was 9.9+/-5.1 ng/mL (mean +/- SD; n = 40). CONCLUSIONS: Although pindolol can accelerate the antidepressant action of selective serotonin reuptake inhibitors in previously untreated patients, it does not elicit a rapid clinical response in treatment-resistant patients within a 10-day period.

Adult↗
PubMed1999

Displacement of the binding of 5-HT(1A) receptor ligands to pre- and postsynaptic receptors by (-)pindolol. A comparative study in rodent, primate and human brain.

Using receptor autoradiography we examined the displacement of the binding of [(3)H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and [(3)H][N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cy clohexanecarboxamide. 3HCl] (WAY 100635) to 5-HT(1A) receptors by (-)pindolol in the brain of four different species, rat, guinea pig, monkey and human. (-)Pindolol completely displaced the binding of both tritiated ligands at 10(-6) M in all species and regions examined. The affinity of (-)pindolol for presynaptic 5-HT(1A) receptors in the dorsal raphe nucleus was similar to that observed in postsynaptic locations, such as hippocampus (areas CA1, CA3 and dentate gyrus) or entorhinal cortex. Affinity values (K(i)) were in the range 3.8 - 15.9 nM for [(3)H]8-OH-DPAT and 5.8 - 22.3 nM for [(3)H]WAY 100635. In human brain, the K(i) values using [(3)H]8-OH-DPAT as ligand were 10.8 nM in the dorsal raphe nucleus and 6.5 - 13.5 in postsynaptic sites. The present data do not support the hypothesis that (-)pindolol may displace 5-HT(1A) ligands preferentially from presynaptic 5-HT(1A) receptors in the dorsal raphe nucleus, as suggested by electrophysiological evidence. The affinity of (-)pindolol for human 5-HT(1A) receptors is below the mean plasma concentration attained in depressed patients treated with a combination of fluoxetine and pindolol, which indirectly supports an action of pindolol at 5-HT(1A) receptors in these patients.

Adrenergic beta-Antagonists↗
PubMed2000

Pindolol occupancy of 5-HT(1A) receptors measured in vivo using small animal positron emission tomography with carbon-11 labeled WAY 100635.

Positron emission tomography (PET), following an intravenous injection of [carbonyl-(11)C]WAY 100635, was used to image central 5-HT(1A) receptors in rat following pretreatment with graded doses of (-)-pindolol (0.001-3 mg/kg, i.v.). The use of PET had advantages over ex vivo radioligand binding methods in that it produced parametric image volumes and reduced errors due to inter-rat variability. Time-radioactivity curves from regions of interest (ROI) acquired from individual rats enabled the estimation of specific binding of the radioligand using a compartmental model with reference tissue input. Binding potential (BP) of [(11)C]WAY 100635 was estimated for frontal cortex and hippocampus (postsynaptic), and midbrain raphe nuclei (presynaptic). In the latter ROI, pindolol dose-dependently decreased BP. The saturation curve could be fitted to a single-site model up to the lowest dose of pindolol used, giving an ED(50) (dose to cause 50% occupancy) value of 0.26 +/- 0. 05 mg/kg, and inclusion of control (nonpindolol-treated) rats did not affect the fit. In contrast, in cortex and hippocampus ROI, low doses of pindolol caused an increase in BP compared with controls. Pindolol doses greater than approximately 0.1 mg/kg, resulted in a dose-dependent decrease in BP, and ED(50) values in cortex and hippocampus were estimated as 0.44 +/- 0.13 and 0.48 +/- 0.12 mg/kg, respectively. The increase in [(11)C]WAY 100635 binding at low pindolol doses is feasibly related to a decrease in basal receptor occupancy following reduced release of endogenous 5-HT. Considering the apparently greater potency of pindolol at the midbrain raphe ROI, this effect could be mediated via agonist activity at the autoreceptor.

Animals↗
PubMed2002

Enantioselectivity in the steady-state pharmacokinetics and transplacental distribution of pindolol at delivery in pregnancy-induced hypertension.

Nine patients taking oral doses of 10 mg/12 h rac-pindolol as part of their treatment for hypertension in pregnancy were recruited for the study. Maternal and fetal gestational age ranged from 20-38 years and 28-41 weeks, respectively. Blood was collected from the umbilical cord vein and from the mother from zero to 12 h after drug administration. Urine was collected for 12 h after rac-pindolol administration at the following intervals: 0-3, 3-6, 6-9, and 9-12 h. Plasma and urine concentrations of the pindolol enantiomers were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The data were fitted to a one-compartment model and differences between (+)-R and (-)-S enantiomers were compared by the paired t-test (P < 0.05). Mean results are reported. The disposition of pindolol in maternal plasma was stereoselective, with higher AUC(SS)0-12 (84.34 vs. 95.69 ng.h/ml) and Cl(R) values (9.16 vs. 10.85 L/h) and lower Vd/f (251.38 vs. 225.17 L) and Cl/f (62.48 vs. 55.74 L/h) for the (+)-R pindolol. The transplacental distribution of pindolol was not stereoselective. Cord, plasma, and presumably fetal, concentrations of the pindolol enantiomers were 56% of the maternal plasma concentrations up to 6 h after the last dose.

Adrenergic beta-Antagonists↗
PubMed1996

Effect of pindolol on hormone secretion and body temperature: partial agonist effects.

Pindolol has been shown to be a partial agonist at 5-HT1A receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT1A partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT1A receptors in man. To determine if pindolol has 5-HT1A agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT1A agonist action and is consistent with a 5-HT1A partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT1A receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT1A-dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by 5-HT1A mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT1A receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.

Adolescent↗
PubMed2005

A mathematical model for paroxetine antidepressant effect time course and its interaction with pindolol.

Although selective 5-HT reuptake inhibitors (SSRIs) block monoamine uptake within hours of administration to patients, their full clinical effect does not appear until 2-4 weeks after treatment onset. Pindolol, a betablocker with weak partial 5-HT1A receptor agonist activity has been shown to produce a more rapid onset of antidepressant action of SSRIs. However, the optimal dosing schedule of pindolol remains controversial. Building on a set-point model described previously for the hypothermic effect of 5-HT agonists, we have developed a model based on the concept of homeostatic control mechanisms, in which SSRIs exert their antidepressant effect by increasing the transduction set-point of the postsynaptic 5-HT1A receptor, and pindolol exerts its effect by increasing the rate of feedback mechanisms. The predictive distribution of the proportion of responders at each day of measurement (based on population simulation from the model) was not significantly different from the proportions observed in two published clinical trials, one with fluoxetine, the other with paroxetine alone or combined with pindolol. The model was applied to the simulation of paroxetine response (clinical score) time course with or without pindolol, after administration of different doses of each drug. The simulated total scores on the MADR scale obtained after treatment with paroxetine alone (20 mg/day) or paroxetine (20 mg/day) with different doses of pindolol (1.5, 7.5 and 37.5 mg/day) support that the reason for inconstant pindolol efficacy is that the 7.5 mg dose is too low. The model might be useful as a basis for clinical trial simulation.

Algorithms↗
PubMed1982

Treatment of angina pectoris with pindolol: the significance of intrinsic sympathomimetic activity of beta blockers.

Although all beta blockers have been found to be effective in the symptomatic relief of angina pectoris, the importance of intrinsic sympathomimetic activity (ISA) has not been studied extensively. In a randomized, double-blind study, we administered equipotent doses of propranolol (10, 20, and 40 mg four times a day) and pindolol (2.5, 5, and 10 mg four times a day), a beta blocker with significant ISA, to 52 patients with angina. Both agents were found to be effective in the treatment of angina. At peak dose, propranolol reduced the number of angina attacks per 2 weeks from 29.29 +/- 4.79 to 18.0 +/- 4.4 (p = 0.021) (a 39% reduction) and increased the exercise tolerance on the treadmill from 7.55 +/- 0.67 METS to 9.36 +/- 0.58 (p = 0.002). Pindolol decreased the number of anginal attacks per 2 weeks from 16.48 +/- 2.63 to 8.65 +/- 2.46 (p = 0.0027) (a 48% reduction) and increased exercise tolerance from 7.95 +/- 0.56 METS to 9.40 +/- 0.57 (p = 0.0245). At the end of the maximum tolerated exercise, propranolol decreased the heart rate from 110.00 +/- 3.41 to 99.71 +/- 3.74 (p = 0.0015). Pindolol also decreased the heart rate at the maximum tolerated exercise from 113.59 +/- 3.24 to 108.12 +/- 3.16 (p = 0.0102). At rest, however, propranolol induced a more pronounced (p = 0.0066) decrease in heart rate (from 69.00 +/- 1.85 to 61.50 +/- 1.99; p = 0.0018), whereas pindolol did not significantly affect the resting heart rate (65.37 +/- 1.47 to 65.5 +/- 1.44; p = 0.9392). In addition propranolol decreased echocardiographically determined ejection fraction from 0.57 +/- 0.02 to 0.15 +/- 0.01 (p = 0.04) and increased the left ventricular end-diastolic volume from 71.8 +/- 3.2 to 92.2 +/- 1.9 ml (p = 0.003), whereas pindolol did not affect the ejection fraction and caused a less pronounced (p = 0.03) increase in end-diastolic volume (from 70.8 +/- 1.8 to 80.2 +/- 2.8; p = 0.02). The data indicate that both propranolol and pindolol are effective in the treatment of angina pectoris and that pindolol decreases the resting heart rate and ejection fraction and increases the left ventricular end-diastolic volume to a lesser extent than propranolol.

Adult↗
PubMed1986

Hemodynamics of metoprolol and pindolol in systemic hypertension with particular reference to reversal of structural vascular changes.

In a double-blind, comparative study metoprolol (100 to 300 mg/day) or pindolol (5 to 15 mg/day) was given in randomized order to 39 patients with uncomplicated essential hypertension. Peripheral hemodynamics were studied by noninvasive means after an initial 6-week placebo period and again after 6 weeks and 6 months of active treatment. Three patients withdrew from the trial during the 6-week period of active treatment. Heart rate during exercise on an ergometric bicycle to a predetermined workload indicated that the degree of beta-adrenoceptor blockade was identical during treatment with either metoprolol or pindolol. Both agents also reduced resting blood pressure to the same extent. Heart rate at rest fell considerably more during metoprolol than pindolol therapy, while vascular resistance was reduced by pindolol but not by metoprolol. This indicates that the antihypertensive effect of metoprolol can be ascribed mainly to cardiac mechanisms; in contrast, pindolol appears to lower blood pressure primarily through vascular effects. Studies at maximal dilatation showed that pindolol, but not metoprolol, reduced resistance at maximal dilatation after 6 months of treatment, indicating that a reversal of the structural vascular changes had occurred. The hemodynamic differences between the 2 agents can probably be explained by the fact that pindolol with its intrinsic sympathomimetic activity acts as a partial agonist causing active stimulation of vascular beta 2 adrenoceptors and relaxation of resistance vessels.

Adult↗
PubMed2006

Pindolol does not augment central serotonin function increases to citalopram in humans: an auditory evoked potential investigation.

Animal studies have demonstrated that the co-administration of pindolol and selective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic functioning to a greater degree than SSRIs alone. However, clinical trials of pindolol augmentation in patients with major depressive disorder have reported contradictory findings, and the central effects of this treatment regime on serotonin functioning in humans are unknown. The current double-blind placebo controlled repeated measures investigation used the loudness dependence auditory evoked potential (LDAEP) to assess central serotonin functioning in healthy participants across three acute treatment conditions: placebo, citalopram (20 mg), and pindolol (10 mg)+citalopram (20 mg). The current paper focuses on the effects of pindolol augmentation of citalopram as compared to the administration of citalopram alone. Enhancement of serotonin function with citalopram in comparison to placebo decreased the slope of the LDAEP (i.e. weaker LDAEP). However, there were no significant differences between the changes in the LDAEP induced by co-administration of pindolol and citalopram compared to citalopram. The present results indicate that, in healthy controls, pindolol augmentation of SSRIs does not potentiate central serotonin function to a greater degree than the administration of an SSRI alone. The findings may provide further support for why pindolol may not be an effective therapeutic strategy to augment serotonin function and antidepressant response.

Adult↗
PubMed1999

Modulation of the firing activity of rat serotonin and noradrenaline neurons by (+/-)pindolol.

BACKGROUND: (+/-)Pindolol is a beta-adrenergic/5-HT1A receptor antagonist used in combination with certain antidepressant drugs to accelerate the onset of the antidepressive response. METHODS: The aim of the present study was to assess, using an in vivo electrophysiologic paradigm, the effect of (+/-)pindolol on the spontaneous firing activity of rat dorsal raphe serotonin (5-HT) and locus coeruleus noradrenaline (NA) neurons. RESULTS: (+/-)Pindolol did not modify the firing activity of dorsal raphe 5-HT neurons at low doses (10 and 200 micrograms/kg, i.v.), but it prevented the suppressant effect of the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD, 10 micrograms/kg, i.v.) but not that of the 5-HT1A receptor 8-hydroxy-N,N-dipropyl-aminotetralin (8-OHDPAT, 5 micrograms/kg, i.v.). At a higher dose (500 micrograms/kg, i.v.), (+/-)pindolol decreased 5-HT neuronal firing and this effect was reversed by the selective 5-HT1A receptor antagonist WAY 100635 (100 micrograms/kg, i.v.), suggesting that it could act as a partial 5-HT1A autoreceptor agonist. In the locus coeruleus, the high dose of (+/-)pindolol decreased the firing activity of NA neurons and this effect was reversed by the 5-HT2A receptor antagonist MDL 100907 (200 micrograms/kg, i.v.). Finally, both a lesion of NA neurons and the administration of MDL 100907 prevented the suppressant effect of (+/-)pindolol on the firing of 5-HT neurons. CONCLUSIONS: It is suggested that, at low doses, (+/-)pindolol acts as a somatodendritic 5-HT1A autoreceptor antagonist whereas at a higher dose, it decreases the tonic excitatory input from NA neurons to 5-HT neurons.

Action Potentials↗