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At least 19 recordsLinked to original sources
PubMed1987

Beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of (S)-pindolol and iodinated (S)-pindolol.

The beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of iodinated (S)-pindolol (IPIN) and (S)-pindolol were investigated in vitro using beta-adrenoceptor binding technique and isolated right atrium (rate increase, beta 1) and uterus (relaxation, beta 2) of the rat. IPIN had a higher affinity towards beta-adrenoceptors compared to (S)-pindolol, with some beta 2-adrenoceptor selectivity. In the rat uterus, IPIN produced only marginal stimulatory effects, while (S)-pindolol caused a concentration-dependent relaxation with a maximal effect that was 55% of that generated by isoprenaline. In the right atrium IPIN caused an increase in the atrial rate similar to that caused by (S)-pindolol. The concentration of IPIN required in the right atrium for a half-maximal response (pD2 = 7.81) was markedly greater than that required for occupation of half the beta-adrenoceptor population (pKB = 9.81). The beta 1-selective blocker metoprolol antagonized the effect of (S)-pindolol and IPIN on the atrial rate but a greater concentration of metoprolol (5 X 10(-6) M compared with 5 X 10(-7) M) was required to antagonize the effect of IPIN significantly. It is concluded that iodination of (S)-pindolol increased its affinity and decreased its efficacy towards beta-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1991

Investigation of the pindolol-Fe(III) complex and its use in the spectrophotometric determination of pindolol in bulk drug and tablets.

It was found that pindolol reacts with Fe(III) chloride producing a green water soluble complex (1:1, v/v) with maximum absorbance at 635 nm. By applying the methods of Sommer and Job [Sommer et al., Folia, tomus XI, Chemia 7, 25, 1970] the conditional stability constant of the complex at pH = 1.70 +/- 0.02 was found to be log K' = 4.95 and the molar absorptivity of the complex to be 206 l mol-1 cm-1. Beer's law was obeyed up to a concentration of 220 mumol l-1 of pindolol. The recoveries were 98-101% (n = 7) and the detection limit was 5 micrograms ml-1. The described method was sufficiently simple, selective and sensitive to be suitable for the rapid and accurate determination of pindolol in tablets.

Ferric Compounds↗
PubMed1977

Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats.

1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.

Administration, Oral↗
PubMed1986

Mode of action of (-)-pindolol on feline and human myocardium.

(-)-Pindolol antagonized competitively and to a similar extent the positive inotropic effects of both (-)-noradrenaline and (-)-adrenaline in human ventricular preparations. An equilibrium dissociation constant KD (-log mol 1(-1) = pKD) of 9.2-9.3 was estimated regardless of disease present or agonist used. (-)-Pindolol antagonized competitively the positive inotropic effects of (-)-adrenaline more than those of (-)-noradrenaline in human atrial preparations. pKD values of (-)-pindolol were 9.6 against (-)-adrenaline and 9.1 against (-)-noradrenaline. The results are consistent with a moderate selectivity of (-)-pindolol for beta 2-compared to beta 1-adrenoceptors in human atrium. (-)-Pindolol competed with [3H]-(-)-bupranolol with a pKD of 9.4 for beta-adrenoceptors of human ventricle. Positive inotropic effects of (-)-pindolol were not detected on human atrium or ventricle in a concentration range of 1-1000 nmol 1(-1). The affinity of (-)-pindolol estimated for human myocardial beta-adrenoceptors, its moderate beta 2-selectivity and its lack of intrinsic activity for contractile force agreed with similar characteristics in other species. (-)-Pindolol caused marked positive chronotropic effects in kitten right atria with an intrinsic activity of 0.5 with respect to catecholamines. On kitten left atria it caused only weak positive inotropic effects with an intrinsic activity of 0.1. (-)-Pindolol (0.6-6000 nmol-1) did not cause positive inotropic effects in kitten papillary muscle. The concentration-effect curve for (-)-pindolol on kitten right and left atria was biphasic. Its positive chronotropic and inotropic effects were not blocked by methysergide, suggesting that 5-hydroxytryptamine (5-HT)-receptors were not involved. Low concentrations of antagonists selective for beta 1- and beta 2-adrenoceptors blocked the high sensitivity component but not the low sensitivity component of the positive chronotropic and inotropic effects. The biphasic nature of the positive chronotropic effects of (-)-pindolol in kitten agreed with previous observations made on guinea-pig right atria and support the concept that 3 receptors in the sinoatrial pacemaker contribute to these chronotropic effects: beta 1, beta 2 and a low-affinity receptor for (-)-pindolol which is neither beta 1 nor beta 2. The partial agonistic activity of (-)-pindolol in the heart appears to be mainly (kitten) or completely (man) restricted to the sinoatrial pacemaker.

Adrenergic beta-Antagonists↗
PubMed1985

Irreversible blockade of beta-adrenergic receptors with a bromoacetyl derivative of pindolol.

A potent irreversible beta-adrenergic derivative of pindolol possessing a chemically reactive group (Br-AAM-pindolol) was synthesized. This compound devoid of agonist properties, competed for all (3H)-dihydroalprenolol (3H-DHA) binding sites in C6 glioma cell and rat cerebellum membranes. Pretreatment of C6 glioma cell membranes with Br-AAM-pindolol and subsequent washing resulted in a time- and dose-dependent blockade of beta-adrenergic receptors. A 50% blockade was achieved in the presence of 1.6 nM Br-AAM-pindolol. This blockade occurs specifically at the beta-adrenergic receptor level, as: 1) it induced a decrease of maximal isoproterenol stimulated adenylate cyclase activity with no modification of basal and sodium fluoride stimulated activity and 2) decreases of (3H)-DHA binding and stimulation of adenylate cyclase activity by the agonist were suppressed in the presence of isoproterenol, a beta-adrenergic agonist. Furthermore, Br-AAM-pindolol treatment did not affect (3H)-diazepam binding in C6 glioma cell membranes. Pretreatment of C6 glioma cells with Br-AAM-pindolol also reduced the response of adenylate cyclase to isoproterenol and the number of beta-adrenergic receptors. The blockade of beta-adrenergic receptors of C6 glioma cells by Br-AAM-pindolol was non-competitive, whereas the blockade obtained with AM-pindolol, a derivative of pindolol devoid of alkylating properties, was competitive. The irreversible blockade of beta-adrenergic receptors by Br-AAM-pindolol in rat erythrocyte membranes was substantiated by the demonstration that no recovery of beta-adrenergic receptors occurred during long term incubation of the membranes (48 h) following Br-AAM-pindolol treatment and subsequent washing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
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↗
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↗
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↗
PubMed1991

Reduction of cardiac hypertrophy in renal hypertensive rabbits with pindolol.

Arterial pressure, cardiac mass and coronary flow reserves were measured in untreated and chronically pindolol-treated rabbits, prepared as either one-kidney one clip (1K1C) hypertensive or uninephrectomized (sham) controls. Pindolol (200 micrograms/kg/day) was administered for either 23 or 30 days, beginning 1 week after, or the day of initial surgery, respectively. Coronary flow was measured, at day 30, using radioactive microspheres, during base-line and adenosine infusion (0.4 mg/kg/min) in anesthetized open-chest preparations. Heart weight of untreated 1K1C animals (9.13 +/- 0.73 g) was significantly greater than the controls (7.19 +/- 0.77 g). Myocardial mass of 1K1C (9.93 +/- 0.86 g) and sham controls (7.40 +/- 0.31 g) were unaffected by chronic pindolol for 23 days. Cardiac hypertrophy was prevented in 1K1C animals treated with pindolol for 30 days (7.53 +/- 1.28 g). Untreated 1K1C animals were hypertensive compared to sham controls (116 +/- 12 and 78 +/- 7 mm Hg) and neither pindolol regime affected blood pressure. Bradycardia was evident in all pindolol-treated animals. Base-line coronary flow was higher in the untreated 1K1C animals compared to untreated controls (228 +/- 43 vs. 182 +/- 31 ml/min/100 g). After chronic pindolol treatments, 1K1C base-line blood flows were reduced (158 +/- 48 and 175 +/- 59 ml/min/100 g, for 23- and 30-day protocols). Adenosine vasodilated flows were not different between the untreated 1K1C and sham animals and were not affected by pindolol treatment. Therefore, hypertension and cardiac hypertrophy were dissociable in this model when pindolol was administered from the onset of hypertension. This suggests immediate involvement of beta adrenergic activation in the development of hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol.

The partial beta adrenoceptor agonist properties of cicloprolol, xamoterol and pindolol have been compared in vivo (anesthetized catecholamine-depleted or pithed rats) and in vitro (guinea pig or rat right atria and guinea pig tracheal muscle preparations) conditions. All three compounds increased heart rate in the former preparations, and their intrinsic activities relative to isoproterenol were 0.7, 0.65 and 0.45, respectively. The positive chronotropic effects of cicloprolol or xamoterol were competitively antagonized by betaxolol or propranolol; however, part of those induced by pindolol were resistant to these beta adrenoceptor antagonists. None of these compounds increased the spontaneous beating rate of isolated guinea pig atria; however, xamoterol only increased heart rate in isolated rat atria, and its intrinsic activity with respect to isoproterenol was 0.4. Pindolol, xamoterol and cicloprolol behaved as competitive beta-1 adrenoceptor antagonists against isoproterenol-induced tachycardia in a pithed rat model. In order to mimic the intrinsic effects of the partial agonist drugs, control dose-response curves for isoproterenol were determined in pithed rats in which the base-line heart rate was elevated by thoracic spinal cord stimulation. In this in vivo preparation, xamoterol and pindolol were more potent beta-1 adrenoceptor antagonists than cicloprolol; however, cicloprolol and xamoterol, in contrast to pindolol, were selective for beta-1 adrenoceptors. In isolated spontaneously beating guinea pig right atria, cicloprolol and xamoterol were equipotent beta-1 adrenoceptor antagonists but were about 50 times less potent than pindolol. In isolated rat atria, the beta-1 adrenoceptor antagonist potency of xamoterol was greater (pA2 = 8.7) than in guinea pig atria (pA2 = 7.8). The potencies of cicloprolol and pindolol did not vary between these species. In catecholamine-depleted rats, high i.v. doses of cicloprolol had vasodilator activity that was partly mediated by beta-2 adrenoceptors. In carbachol-contracted guinea pig trachea, cicloprolol and xamoterol, in contrast to pindolol, were relatively inactive against isoproterenol-induced relaxation. In conclusion, cicloprolol and xamoterol, similarly to pindolol, behave as agonists and antagonists of beta-1 adrenoceptors. However, only cicloprolol and xamoterol show an elevated degree of selectivity toward the beta-1 adrenoceptor subtype.

Adrenergic beta-Agonists↗
PubMed1986

Effective termination of reentrant supraventricular tachycardia by single dose oral combination therapy with pindolol and verapamil.

We evaluated the efficacy of single oral dose combining 20 mg pindolol and 120 mg verapamil in termination of paroxysmal supraventricular tachycardia (SVT) in 12 patients with recurrent symptomatic tachycardia. All had electrically inducible SVT lasting longer than 30 minutes. Patients were administered placebo or crushed pindolol and verapamil on 2 consecutive days after tachycardia was electrically induced and allowed to sustain for 30 minutes. With placebo, SVT lasted 186 +/- 18 minutes (mean +/- SEM); five patients converted spontaneously within 121 to 180 minutes. With pindolol and verapamil, 9 of 12 patients (responders) converted to sinus rhythm within 8 to 74 minutes. The mean duration of SVT in the nine responders was 28 +/- 8 minutes compared with 168 +/- 20 minutes on placebo (p less than 0.001). Before termination, tachycardia rate on pindolol and verapamil slowed significantly from 182 +/- 5 to 164 +/- 7/min (p less than 0.05) compared with no significant change in the rate of SVT on placebo. The mean systolic blood pressure during tachycardia was 97 +/- 5 mm Hg with placebo and 101 +/- 7 mm Hg with pindolol and verapamil. Serum levels of pindolol and verapamil obtained in seven patients at time of spontaneous termination of tachycardia were 66 +/- 13 and 56 +/- 14 ng/ml, respectively. The side effects with pindolol and verapamil included lightheadedness in one patient and symptoms of rapid palpitations in three. A single oral dose of pindolol and verapamil is safe and effective in termination of acute paroxysmal SVT and may be the initial therapy of choice in selected patients.

Adult↗
PubMed1985

The sympathomimetic activity of (+/-)-pindolol at beta 1- and beta 2-adrenoceptor sites.

In isolated right atrial and stilboestrol-pretreated uterine preparations from both guinea-pigs and rats, pindolol elicited propranolol-sensitive positive chronotropic and smooth muscle relaxant actions. Although the pD2 values for pindolol (8.4-9.2) and (-)-isoprenaline (ISO, 8.4-8.7) fell within the same range in these preparations, the maximum responses to pindolol were less than 15% of those to the catecholamine. Thus, pindolol did not display any selectivity for agonistic actions at beta 1- or beta 2-adrenoceptors. In uteri taken from progesterone-pretreated rats, the pD2 value for (-)-isoprenaline was 9.5 and that of pindolol 8.5. In these preparations the maximal relaxant effect of pindolol (approximately 50% Emax ISO) was greater than that found in oestrogen-pretreated uteri. Thus, it appears that the maximal response of pindolol in vitro can be related to the pD2 value for (-)-isoprenaline. In anesthetized cats, intravenous pindolol elicited non-beta-adrenoceptor-mediated increases in heart rate and decreases in soleus muscle contractility. The mechanism(s) underlying the latter actions are unknown.

Anesthesia↗