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Chemical Compound Review

pindolol     1-(1H-indol-4-yloxy)-3- (propan-2...

Synonyms: Blocklin, Decreten, Pinbetol, Pynastin, Prindolol, ...
 
 
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Disease relevance of pindolol

  • Pindolol and hyperthyroidism [1].
  • 50 patients with confirmed hypertension were treated with endralazine, a new peripheral vasodilator, in addition to the beta-blocker, pindolol, to which they had not responded adequately [2].
  • The mean baseline plasma norepinephrine concentration for the population was 609 +/- 172 pg/ml (normal = 196 +/- 7 pg/ml) and was markedly elevated in two patients (931 and 2053 pg/ml) who developed severe pindolol-induced hypotension [3].
  • Thus we investigated the relationship between plasma catecholamine concentrations and the hemodynamic effect of pindolol (an index of sympathetic vascular tone) in 10 patients with cirrhosis [4].
  • Lack of efficacy of pindolol in tardive dyskinesia [5].
 

Psychiatry related information on pindolol

 

High impact information on pindolol

  • The treatment of patients with major depression using an SSRI and pindolol, a 5-HT1A/ beta-adrenoceptor antagonist, markedly reduced the latency of the antidepressant response in previously untreated patients and induced a rapid improvement in treatment-resistant patients [11].
  • The slopes of the resting heart rate vs. the plasma concentration of l-pindolol were significantly less than zero and were significantly correlated to the pretreatment heart rate, which supports the hypothesis that intrinsic sympathetic tone largely determines the effect of pindolol on the resting heart rate [12].
  • Selective serotonin reuptake inhibitors plus pindolol. The REEP [13].
  • Alberto Kaumann suggests that such non-conventional partial agonists, often analogues of pindolol, may act through a third heart beta-adrenoceptor, which resembles the beta 3-adrenoceptor of white adipocytes and smooth muscle of airways and ileum [14].
  • With pindolol, the fall in blood pressure was associated with a fall in vascular resistance (26 +/- 6%), whereas with propranolol, it was predominantly associated with a fall in cardiac output (11 +/- 7%) [15].
 

Chemical compound and disease context of pindolol

  • A beta-blocker (pindolol) and a diuretic (clopamide) were given in different dosages, singly and in two different combinations, to 71 patients with mild to moderate essential hypertension [16].
  • The antihypertensive effect of intravenous (acute) and oral (long-term) beta-adrenergic blockade with propranolol or pindolol was evaluated in 46 male patients with either borderline (group I; 23 patients) or sustained (group II; 23 patients) essential hypertension [17].
  • Chronic effects of labetalol, pindolol, and propranolol on calf blood flow in intermittent claudication [18].
  • The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation [19].
  • Our objective was to determine whether the selective beta blocker, metoprolol, or the nonselective intrinsic sympathomimetic activity (ISA)-blocker pindolol, reduce infarct size as a function of an area at risk (AR) in a permanent infarction model in dogs and which blocker is preferable in regards to myocardial function [20].
 

Biological context of pindolol

  • With pindolol, mean arterial pressure was reduced (p less than 0.05) 1 hour after administration, whereas the cardiac index and the systemic vascular resistance index did not change [21].
  • The rest and exercise hemodynamic-inotropic response to administration of the beta-blocker pindolol was evaluated in 10 patients with congestive cardiomyopathy to determine whether the intrinsic sympathomimetic activity (ISA) of this agent may preserve ventricular function in the setting of beta-blockade [3].
  • After pindolol administration, individual hemodynamic changes (cardiac index, systemic vascular resistance, wedged hepatic venous pressure) were significantly correlated with plasma catecholamine concentrations [4].
  • This increase in fractional shortening suggests the possibility that the partial agonist or intrinsic sympathomimetic activity of pindolol may play a role in preserving left ventricular function in patients with borderline or impaired function [22].
  • [3H]5-HT binding was performed in the presence of 100 nM pindolol, which is inactive at 5-ht7 receptors but prevents the binding of [3H]5-HT to 5-HT1A and 5-HT1B receptor binding sites [23].
 

Anatomical context of pindolol

  • Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 microM of selected beta-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37 degrees C for 10 minutes [24].
  • Systemic and splanchnic hemodynamics and plasma catecholamine concentrations in the pulmonary artery and the splanchnic veins (hepatic and azygos veins) were studied before and after the oral administration of pindolol (20 mg) [4].
  • Alone and in combination, we observed a significant increase in basal and pindolol-stimulated cAMP accumulation in COS-7 cells transiently transfected with the mutant receptors [25].
  • Previous investigators have probed the effects of pindolol on serotonergic dorsal raphe cell firing in animal species; here we confirm their findings and extend them to include observations on postsynaptic 5-HT(1A) receptors in the hippocampus [26].
  • BACKGROUND: The ability of pindolol to block 5-HT(1A) autoreceptors on serotonin-containing neurons in the raphe nuclei is thought to underlie the clinical reports of enhanced efficacy and rate of improvement in depressed patients treated with pindolol/selective serotonin reuptake inhibitor (SSRI) combinations [26].
 

Associations of pindolol with other chemical compounds

 

Gene context of pindolol

  • [18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge [32].
  • Two binding sites were detected in the presence of 1 microM pindolol (to block 5-HT1A and 5-HT1B receptors), and 100 nM mesulergine (to block 5-HT1C and 5-HT2 receptors) [33].
  • While the data are consistent with 5-HT1A receptor mediation of PRL and GH responses to LTP, the intrinsic sympathomimetic actions of pindolol might also be involved in the attenuation of the endocrine responses to LTP [34].
  • Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test [35].
  • 6 LCAT activity was significantly higher (P less than 0.01) during pindolol treatment than after the break in it [36].
 

Analytical, diagnostic and therapeutic context of pindolol

References

  1. Pindolol and hyperthyroidism. Abadie, E., Leclercq, J.F., Passa, P. N. Engl. J. Med. (1983) [Pubmed]
  2. Endralazine, a new peripheral vasodilator: absence of effect of acetylator status on antihypertensive effect. Holmes, D.G., Bogers, W.A., Wideroe, T.E., Huunan-Seppala, A., Wideroe, B. Lancet (1983) [Pubmed]
  3. Hemodynamic-inotropic response to beta-blocker with intrinsic sympathomimetic activity in patients with congestive cardiomyopathy. Binkley, P.F., Lewe, R.F., Lima, J.J., Al-Awwa, A., Unverferth, D.V., Leier, C.V. Circulation (1986) [Pubmed]
  4. Plasma catecholamine concentrations are a reliable index of sympathetic vascular tone in patients with cirrhosis. Braillon, A., Gaudin, C., Poo, J.L., Moreau, R., Debaene, B., Lebrec, D. Hepatology (1992) [Pubmed]
  5. Lack of efficacy of pindolol in tardive dyskinesia. Greendyke, R.M., Webster, J.C., Kim, J., Kim, H. The American journal of psychiatry. (1988) [Pubmed]
  6. Central nervous system effects of beta-adrenergic-blocking drugs: the role of ancillary properties. Kostis, J.B., Rosen, R.C. Circulation (1987) [Pubmed]
  7. Pindolol potentiation of paroxetine for generalized social phobia: a double-blind, placebo-controlled, crossover study. Stein, M.B., Sareen, J., Hami, S., Chao, J. The American journal of psychiatry. (2001) [Pubmed]
  8. Neuroleptic-induced akathisia treated with pindolol. Reiter, S., Adler, L., Erle, S., Duncan, E. The American journal of psychiatry. (1987) [Pubmed]
  9. Adverse effects of pindolol augmentation in patients with bipolar depression. Yatham, L.N., Lint, D., Lam, R.W., Zis, A.P. Journal of clinical psychopharmacology. (1999) [Pubmed]
  10. Mitchell B. Balter Award--1998. Pindolol and major affective disorders: a three-year follow-up study of 30,485 patients. Räsänen, P., Hakko, H., Tiihonen, J. Journal of clinical psychopharmacology. (1999) [Pubmed]
  11. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Artigas, F., Romero, L., de Montigny, C., Blier, P. Trends Neurosci. (1996) [Pubmed]
  12. Stereoselective renal clearance of pindolol in humans. Hsyu, P.H., Giacomini, K.M. J. Clin. Invest. (1985) [Pubmed]
  13. Selective serotonin reuptake inhibitors plus pindolol. The REEP. Bordet, R., Thomas, P., Dupuis, B. Lancet (1997) [Pubmed]
  14. Is there a third heart beta-adrenoceptor? Kaumann, A.J. Trends Pharmacol. Sci. (1989) [Pubmed]
  15. Hemodynamic and beta-adrenergic receptor adaptations during long-term beta-adrenoceptor blockade. Studies with acebutolol, atenolol, pindolol, and propranolol in hypertensive patients. van den Meiracker, A.H., Man in't Veld, A.J., Boomsma, F., Fischberg, D.J., Molinoff, P.B., Schalekamp, M.A. Circulation (1989) [Pubmed]
  16. New design for clinical trial of antihypertensive drugs applied to pindolol, clopamide, and combinations thereof. Nyberg, G., Asplund, J., Anagreus, N., Aström, B., Leppert, J., Bergström, R., Overmo, J., Kullman, S., Lessem, J. Lancet (1982) [Pubmed]
  17. Acute and long-term studies of the mechanisms of action of beta-blocking drugs in lowering blood pressure. Stumpe, K.O., Kolloch, R., Vetter, H., Gramann, W., Krück, F., Ressel, C., Higuchi, M. Am. J. Med. (1976) [Pubmed]
  18. Chronic effects of labetalol, pindolol, and propranolol on calf blood flow in intermittent claudication. Lepäntalo, M. Clin. Pharmacol. Ther. (1985) [Pubmed]
  19. Improved control of atrial fibrillation with combined pindolol and digoxin therapy. James, M.A., Channer, K.S., Papouchado, M., Rees, J.R. Eur. Heart J. (1989) [Pubmed]
  20. Failure of pindolol and metoprolol to reduce the size of non-reperfused infarcts in dogs using area at risk techniques. Lange, R., Nieminen, M.S., Kloner, R.A. Cardiovasc. Res. (1984) [Pubmed]
  21. Hemodynamic and hormonal adaptations to beta-adrenoceptor blockade. A 24-hour study of acebutolol, atenolol, pindolol, and propranolol in hypertensive patients. van den Meiracker, A.H., Man in 't Veld, A.J., van Eck, H.J., Boomsma, F., Schalekamp, M.A. Circulation (1988) [Pubmed]
  22. Improvement in depressed cardiac function in hypertensive patients during pindolol treatment. Plotnick, G.D., Fisher, M.L., Wohl, B., Hamilton, J.H., Hamilton, B.P. Am. J. Med. (1984) [Pubmed]
  23. Identification of 5-hydroxytryptamine7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant treatment. Sleight, A.J., Carolo, C., Petit, N., Zwingelstein, C., Bourson, A. Mol. Pharmacol. (1995) [Pubmed]
  24. Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. Mak, I.T., Weglicki, W.B. Circ. Res. (1988) [Pubmed]
  25. Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. Ballesteros, J.A., Jensen, A.D., Liapakis, G., Rasmussen, S.G., Shi, L., Gether, U., Javitch, J.A. J. Biol. Chem. (2001) [Pubmed]
  26. 5-HT(1A) agonist potential of pindolol: electrophysiologic studies in the dorsal raphe nucleus and hippocampus. Sprouse, J., Braselton, J., Reynolds, L. Biol. Psychiatry (2000) [Pubmed]
  27. Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors. Levi, R., Zavecz, J.H. Circ. Res. (1979) [Pubmed]
  28. Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro. Stanford, I.M., Lacey, M.G. J. Neurosci. (1996) [Pubmed]
  29. Cardioselective and nonselective beta-adrenoceptor blocking drugs in hypertension: a comparison of their effect on blood pressure during mental and physical activity. Floras, J.S., Hassan, M.O., Jones, J.V., Sleight, P. J. Am. Coll. Cardiol. (1985) [Pubmed]
  30. Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity. Serretti, A., Zanardi, R., Rossini, D., Cusin, C., Lilli, R., Smeraldi, E. Mol. Psychiatry (2001) [Pubmed]
  31. Measurement of partial agonist activity of pindolol. Carruthers, S.G., Twum-Barima, Y. Clin. Pharmacol. Ther. (1981) [Pubmed]
  32. [18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge. Pinborg, L.H., Adams, K.H., Yndgaard, S., Hasselbalch, S.G., Holm, S., Kristiansen, H., Paulson, O.B., Knudsen, G.M. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  33. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. Leonhardt, S., Herrick-Davis, K., Titeler, M. J. Neurochem. (1989) [Pubmed]
  34. Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan. Smith, C.E., Ware, C.J., Cowen, P.J. Psychopharmacology (Berl.) (1991) [Pubmed]
  35. Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test. Bourin, M., Redrobe, J.P., Baker, G.B. Psychopharmacology (Berl.) (1998) [Pubmed]
  36. Effect of pindolol on serum lipids and lipid metabolizing enzymes. Lehtonen, A., Hietanen, E., Marniemi, J., Peltonen, P., Niskanen, J. British journal of clinical pharmacology. (1982) [Pubmed]
  37. Drug therapy. Pindolol: a new beta-adrenoceptor antagonist with partial agonist activity. Frishman, W.H. N. Engl. J. Med. (1983) [Pubmed]
  38. No effect of Pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study. Dejgård, A., Hilsted, J. Diabetologia (1988) [Pubmed]
  39. Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low. Rabiner, E.A., Bhagwagar, Z., Gunn, R.N., Sargent, P.A., Bench, C.J., Cowen, P.J., Grasby, P.M. The American journal of psychiatry. (2001) [Pubmed]
  40. Beta-adrenergic receptor blocking drugs in spontaneous hypertension. Levy, J.V. Am. J. Med. (1976) [Pubmed]
 
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