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The Journal of Pharmacology and... May 1993Recently, we found that the beta 1/beta 2 adrenoceptor blocking agent (-)penbutolol prevents behavioral and biochemical actions of the specific serotonin (5-HT)1A...
Recently, we found that the beta 1/beta 2 adrenoceptor blocking agent (-)penbutolol prevents behavioral and biochemical actions of the specific serotonin (5-HT)1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. The putative 5-HT1 receptor antagonist profile of (-)penbutolol was further explored in the present study, using in vivo microdialysis methods to assess its effects on central 5-HT release. (+)Penbutolol and (-)pindolol were included for comparison purposes. In contrast to (-)pindolol (8.0 mg/kg s.c.), administration of (-)penbutolol (2.0 or 8.0 mg/kg s.c.) increased hippocampal 5-HT output. The (-)penbutolol-induced 5-HT response was dose-related, stereoselective and Ca(++)-dependent. In addition, the 5-HT response to (-)penbutolol was abolished by omitting the 5-HT reuptake blocker citalopram from the perfusion medium, suggesting the need for endogenous 5-HT tone. Local (-)penbutolol (1 microM) perfusion increased the 5-HT output per se, and also blocked 5-HT release suppression caused by the 5-HT1B receptor agonist CP-93,129. Furthermore, (-)penbutolol, but not its (+)antipode, prevented the decrease of 5-HT release induced by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. By comparison, the 5-HT1 receptor inactive beta adrenoceptor blockers metoprolol (beta 1) and ICI 118,551 (beta 2), given alone or in combination, did not increase 5-HT output and were ineffective in antagonizing the (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin response. The data indicate that (-)penbutolol possesses 5-HT1A and 5-HT1B autoreceptor antagonist properties, and may be a useful tool in studies of central 5-HT receptor-mediated function.
Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adrenergic beta-Antagonists; Animals; Citalopram; Dialysis; Hippocampus; Male; Metoprolol; Penbutolol; Perfusion; Pindolol; Propanolamines; Pyridines; Pyrroles; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Stereoisomerism
PubMed: 8098761
DOI: No ID Found -
Penbutolol in hypertension, alone and in combination with furosemide. A long-term multicentre study.South African Medical Journal =... Jan 1983Penbutolol is a new, potent and long-acting non-cardioselective beta-adrenergic blocker which has been evaluated in a 6-month open study of patients with moderate... (Clinical Trial)
Clinical Trial
Penbutolol is a new, potent and long-acting non-cardioselective beta-adrenergic blocker which has been evaluated in a 6-month open study of patients with moderate essential or renal hypertension. Eighty-two patients entered the study and 69 completed at least 3 months of treatment. Two-thirds of these showed a good response to penbutolol given alone as a single daily dose of either 40 mg or 80 mg. The major reduction in blood pressure occurred within the first 2 weeks of active therapy. This response was maintained for the entire study period. Blood pressure reduction after penbutolol did not correlate wtih the small reduction in heart rate observed. The remaining patients were treated with a combination of penbutolol and furosemide and most had achieved satisfactory control of their blood pressure by the end of the study. Penbutolol was well tolerated and produced no serious adverse effects. Some patients developed gastro-intestinal side-effects at the beginning of treatment which subsequently resolved. One patient with chronic glomerulonephritis showed a marked deterioration in renal function during the study. This may well have been related to disease progression. No other significant changes in biochemical or haematological parameters were observed.
Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Drug Therapy, Combination; Female; Furosemide; Heart Rate; Humans; Hypertension; Male; Middle Aged; Penbutolol; Propanolamines; Tears
PubMed: 6336854
DOI: No ID Found -
South African Medical Journal =... Mar 1986A single-blind placebo-controlled study was conducted on black hypertensive patients with a once-daily dose of penbutolol (Betapressin; Hoechst); a non-selective... (Clinical Trial)
Clinical Trial
A single-blind placebo-controlled study was conducted on black hypertensive patients with a once-daily dose of penbutolol (Betapressin; Hoechst); a non-selective beta-blocker. Of 29 patients who participated in a 4-week run-in period, 18 were entered into a 20-week trial of the active medication. Fourteen patients were adequately controlled, 2 did not respond satisfactorily and 2 dropped out of the study. On cessation of therapy all patients became hypertensive again. No significant changes in mean heart rates were observed during active medication as opposed to placebo. Penbutolol can therefore be used as a sole antihypertensive agent in blacks.
Topics: Adult; Black People; Blood Pressure; Clinical Trials as Topic; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Penbutolol; Propanolamines; Time Factors
PubMed: 3515587
DOI: No ID Found -
British Journal of Clinical Pharmacology Jun 1977Eleven patients with spinal canal block from metastatic epidural tumor, documented with Pantopaque myelography, were given an additional injection of up to 5 cc of air.... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Eleven patients with spinal canal block from metastatic epidural tumor, documented with Pantopaque myelography, were given an additional injection of up to 5 cc of air. This technique forced contrast material past the block in 10 of 11 cases. It failed in one case in which symptoms had been present for 19 days. Air injection allowed visualization of more cephalad lesions and defined the superior extent of the initial obstructing lesion without the need for a lateral cervical or cisternal puncture. It caused transient discomfort but no neurologic deterioration. This technique is less painful, requires less patient cooperation, expedites localization, and does not require the special skills needed for cervical puncture.
Topics: Adrenergic beta-Antagonists; Cyclopentanes; Humans; Kinetics; Physical Exertion; Propanolamines; Propranolol; Pulse; Time Factors
PubMed: 20121
DOI: 10.1111/j.1365-2125.1977.tb00734.x -
South African Medical Journal =... Jun 1986
Clinical Trial
Topics: Black People; Clinical Trials as Topic; Humans; Hypertension; Penbutolol; Propanolamines
PubMed: 3520882
DOI: No ID Found -
Minerva Medica Sep 1987Penbutolol has proved particularly effective and suitable for the treatment, even on a long-term basis, of recently developed hypertension, especially in its...
Penbutolol has proved particularly effective and suitable for the treatment, even on a long-term basis, of recently developed hypertension, especially in its hyperkinetic forms. The drug produces minimal side effects, is well tolerated and gives an early therapeutic response. In addition penbutolol does not cause any significant alterations in the biohumoral parameters of the patients treated and is ideal for combination with dihydralazine, reserpine and dihydrochlorotiazide in the treatment of more stubborn cases, making it possible to reduce the doses of the other drugs without causing bradycardia.
Topics: Blood Pressure; Diabetes Complications; Dihydralazine; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hyperlipidemias; Hypertension; Hyperthyroidism; Male; Penbutolol; Propanolamines; Reserpine
PubMed: 3658210
DOI: No ID Found -
The American Journal of Cardiology Jun 1989Dose-response relations with penbutolol--a beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to... (Clinical Trial)
Clinical Trial Comparative Study
Dose-response relations with penbutolol--a beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to moderate hypertension (untreated supine diastolic blood pressure [BP] greater than or equal to 95 and less than or equal to 115 mm Hg). Penbutolol was administered once daily in 10, 20 or 40 mg doses for 6 weeks and compared with placebo. Mean declines from baseline in supine diastolic BP were comparable in the 3 penbutolol treatment groups and significantly superior to placebo (p less than 0.05). A significant difference between penbutolol dosage groups was observed only for supine systolic BP; the mean decline at 20 mg/day was significantly larger than that at 10 mg/day (p less than 0.05). Maximum BP response developed in approximately 4 weeks at 10 mg/day and in 2 weeks at the higher dosages. Decline in mean heart rate after 6 weeks of penbutolol therapy significantly exceeded placebo only at 40 mg/day (7.2 vs 2.5 beats/min, p less than 0.05). Treatment was well-tolerated and discontinued because of adverse effects in only 7 patients receiving penbutolol and 3 receiving placebo. The lack of significant bradycardia and the low incidence of other troublesome adverse effects are potential advantages during antihypertensive therapy with penbutolol. With rapid onset of effect and good efficacy and tolerability, the 20 mg once-daily dose appears to be optimum for therapy with this new agent.
Topics: Blood Pressure; Double-Blind Method; Drug Administration Schedule; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Multicenter Studies as Topic; Penbutolol; Placebos; Propanolamines; Random Allocation
PubMed: 2658525
DOI: 10.1016/0002-9149(89)91045-x -
Pharmatherapeutica 1989A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Chlorides; Creatinine; Double-Blind Method; Exercise; Humans; Male; Penbutolol; Propanolamines; Pulse; Sodium; Urodynamics; Vasopressins
PubMed: 2526341
DOI: No ID Found -
European Journal of Clinical... 1982Penbutolol (Hoe 893d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I-II. The... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Penbutolol (Hoe 893d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I-II. The dose (50-100mg) needed to achieve the therapeutic goal, i.e. supine diastolic BP less than 95 mm Hg, was titrated individually. On a daily dose of penbutolol 83 +/- 19 mg (mean +/- SD) blood pressure (BP, mean +/- SD) fell from 180 +/- 21/112 +/- 8 mmHg on placebo to 154 +/- 25/94 +/- 14 mmHg. 18 patients who reached the therapeutic goal (responders) continued in a double blind, cross-over study versus placebo, during which the supine BP fell on average 20/10 mmHg on the same dose of penbutolol, and 2/1 mmHg on placebo. Plasma concentrations (mean +/- SD) of free 0.10 +/- 0.07 microgram/ml) and total (2.02 +/- 1.39 microgram/ml) penbutolol did not differ between responders and nonresponders, and were not correlated with the fall in BP. Side effects were mild and mostly well tolerated. One patient developed dermatitis and another an elevation of liver enzymes.
Topics: Adult; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Penbutolol; Propanolamines; Time Factors
PubMed: 7047173
DOI: 10.1007/BF00542451 -
British Journal of Pharmacology May 1999The antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) might be enhanced by co-administration of 5-HT1A receptor antagonists. Thus, we have...
Effects of (-)-tertatolol, (-)-penbutolol and (+/-)-pindolol in combination with paroxetine on presynaptic 5-HT function: an in vivo microdialysis and electrophysiological study.
The antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) might be enhanced by co-administration of 5-HT1A receptor antagonists. Thus, we have recently shown that the selective 5-HT1A receptor antagonist, WAY 100635, blocks the inhibitory effect of an SSRI on 5-HT cell firing, and enhances its ability to elevate extracellular 5-HT in the forebrain. Here we determined whether the beta-adrenoceptor/5-HT1A receptor ligands (+/-)-pindolol, (-)-tertatolol and (-)-penbutolol, interact with paroxetine in a similar manner. Both (-)-tertatolol (2.4 mg kg(-1) i.v.) and (-)-penbutolol (2.4 mg kg(-1) i.v.) enhanced the effect of paroxetine (0.8 mg kg(-1) i.v.) on extracellular 5-HT in the frontal cortex, whilst (+/-)-pindolol (4 mg kg(-1) i.v.) did not. (-)-Tertatolol (2.4 mg kg(-1) i.v.) alone caused a slight increase in 5-HT however, (-)-penbutolol (2.4 mg kg(-1) i.v.) alone had no effect. In electrophysiological studies (-)-tertatolol (2.4 mg kg(-1) i.v.) alone had no effect on 5-HT cell firing but blocked the inhibitory effect of paroxetine. In contrast, (-)-penbutolol (0.1-0.8 mg kg(-1) i.v.) itself inhibited 5-HT cell firing, and this effect was reversed by WAY 100635 (0.1 mg kg(-1) i.v.). We have recently shown that (+/-)-pindolol inhibits 5-HT cell firing via a WAY 100635-sensitive mechanism. Our data suggest that (-)-tertatolol enhances the effect of paroxetine on forebrain 5-HT via blockade of 5-HT1A autoreceptors which mediate paroxetine-induced inhibition of 5-HT cell firing. In comparison, the mechanisms by which (-)-penbutolol enhances the effect of paroxetine on extracellular 5-HT is unclear, since (-)-penbutolol itself appears to have agonist properties at the 5-HT1A autoreceptor. Indeed, the agonist action of (+/-)-pindolol at 5-HT1A autoreceptors probably explains its inability to enhance the effect of paroxetine on 5-HT in the frontal cortex. Overall, our data suggest that both (-)-tertatolol and (-)-penbutolol are superior to (+/-)-pindolol in terms of enhancing the effect of an SSRI on extracellular 5-HT. Both (-)-tertatolol and (-)-penbutolol are worthy of investigation for use as adjuncts to SSRIs in the treatment of major depression.
Topics: Adrenergic beta-Antagonists; Animals; Antidepressive Agents; Drug Synergism; Electrophysiology; In Vitro Techniques; Male; Membrane Potentials; Microdialysis; Paroxetine; Patch-Clamp Techniques; Penbutolol; Pindolol; Propanolamines; Prosencephalon; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Receptors, Presynaptic; Receptors, Serotonin; Serotonin; Selective Serotonin Reuptake Inhibitors; Thiophenes
PubMed: 10369467
DOI: 10.1038/sj.bjp.0702546