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{{Short description|Chemical compound}}
{{Short description|Chemical compound}}
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{{Infobox drug
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'''Pindolol''', sold under the brand name '''Visken''' among others, is a nonselective [[beta blocker]] which is used in the treatment of [[hypertension]].<ref name="Drugs.com">Drugs.com [https://www.drugs.com/international/pindolol.html International brand names for pindolol] {{webarchive|url=https://web.archive.org/web/20171001214241/https://www.drugs.com/international/pindolol.html |date=2017-10-01 }} Page accessed Sept 4, 2015</ref><ref name="Cochrane">{{cite journal | last1 = Wong | first1 = GW | last2 = Boyda | first2 = HN | last3 = Wright | first3 = JM | date = Nov 2014 | title = Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension | journal = Cochrane Database Syst Rev | volume = 11 | issue = 11| page = CD007450 | doi = 10.1002/14651858.CD007450.pub2 | pmid = 25427719 | pmc = 6486122 }}</ref> It is also an [[receptor antagonist|antagonist]] of the [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]], preferentially blocking [[inhibitory postsynaptic potential|inhibitory]] 5-HT<sub>1A</sub> [[autoreceptor]]s, and has been researched as an [[adjunct therapy|add-on therapy]] to [[selective serotonin reuptake inhibitor]]s (SSRIs) in the treatment of [[depression (mood)|depression]].<ref name="pmid9635544" /><ref name="pmid23757185" /><ref name="pmid25689398" />
'''Pindolol''', sold under the brand name '''Visken''' among others, is a nonselective [[beta blocker]] which is used in the treatment of [[hypertension]].<ref name="Drugs.com">Drugs.com [https://www.drugs.com/international/pindolol.html International brand names for pindolol] {{webarchive|url=https://web.archive.org/web/20171001214241/https://www.drugs.com/international/pindolol.html |date=2017-10-01 }} Page accessed Sept 4, 2015</ref><ref name="Cochrane">{{cite journal | vauthors = Wong GW, Boyda HN, Wright JM | title = Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 11 | pages = CD007450 | date = November 2014 | pmid = 25427719 | pmc = 6486122 | doi = 10.1002/14651858.CD007450.pub2 }}</ref> It is also an [[receptor antagonist|antagonist]] of the [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]], preferentially blocking [[inhibitory postsynaptic potential|inhibitory]] 5-HT<sub>1A</sub> [[autoreceptor]]s, and has been researched as an [[adjunct therapy|add-on therapy]] to various antidepressants, such as [[clomipramine]] and the [[selective serotonin reuptake inhibitor]]s (SSRIs), in the treatment of [[depression (mood)|depression]]<ref name="pmid9635544" /><ref name="pmid23757185" /><ref name="pmid25689398" /> and [[obsessive-compulsive disorder]].<ref>Mundo, Emanuela, Emanuela Guglielmo, and Laura Bellodi. "Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double blind, placedo-controlled study." International clinical psychopharmacology 13, no. 5 (1998): 219-224.</ref><ref>Sassano-Higgins, S.A. and Pato, M.T., 2015. Pindolol augmentation of selective serotonin reuptake inhibitors and clomipramine for the treatment of obsessive-compulsive disorder: A meta-analysis. Journal of Pharmacology and Pharmacotherapeutics, 6(1), pp.36-38.</ref>


==Medical uses==
==Medical uses==
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{{See also|Beta blocker#Contraindications|Propranolol#Contraindications}}
{{See also|Beta blocker#Contraindications|Propranolol#Contraindications}}


Similar to propranolol with an extra contraindication for hyperthyroidism. In patients with thyrotoxicosis, possible deleterious effects from long-term use of pindolol have not been adequately appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or complications, and give a false impression of improvement. Therefore, abrupt withdrawal of pindolol may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.<ref name=rx>{{cite web |url=http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20V%29/VISKEN.html |title=Archived copy |access-date=2010-08-15 |url-status=live |archive-url=https://web.archive.org/web/20110927181138/http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20V)/VISKEN.html |archive-date=2011-09-27 }}</ref>
Similar to propranolol with an extra contraindication for hyperthyroidism. In patients with thyrotoxicosis, possible deleterious effects from long-term use of pindolol have not been adequately appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or complications, and give a false impression of improvement. Therefore, abrupt withdrawal of pindolol may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.<ref name=rx>{{cite web |url=http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20V%29/VISKEN.html |title=RxMed: Pharmaceutical Information - VISKEN |access-date=2010-08-15 |url-status=live |archive-url=https://web.archive.org/web/20110927181138/http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20V)/VISKEN.html |archive-date=2011-09-27 }}</ref>


Pindolol has [[intrinsic sympathomimetic activity]] and is therefore used with caution in [[angina pectoris]].<ref name=rx/>
Pindolol has [[intrinsic sympathomimetic activity]] and is therefore used with caution in [[angina pectoris]].<ref name=rx/>
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===Pharmacodynamics===
===Pharmacodynamics===
{| class="wikitable floatleft" style="font-size:small;"
{| class="wikitable floatleft" style="font-size:small;"
|+ Pindolol<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth| author1 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2212&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>
|+ Pindolol<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth| vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2212&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>
|-
|-
! Site !! K<sub>i</sub> (nM) !! Species !! Ref
! Site !! K<sub>i</sub> (nM) !! Species !! Ref
|-
|-
| '''[[5-HT1A receptor|5-HT<sub>1A</sub>]]''' || '''15–81''' || '''Human''' || <ref name="pmid2078271">{{cite journal | vauthors = Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolaños F, Schechter L, Gozlan H | title = The main features of central 5-HT1 receptors | journal = Neuropsychopharmacology | volume = 3 | issue = 5–6 | pages = 349–60 | year = 1990 | pmid = 2078271 }}</ref><ref name="pmid1565658">{{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR | title = Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 8 | pages = 3630–4 | year = 1992 | pmid = 1565658 | pmc = 48922 | doi = 10.1073/pnas.89.8.3630| bibcode = 1992PNAS...89.3630W | doi-access = free }}</ref><ref name="pmid17804228">{{cite journal | vauthors = Krushinski JH, Schaus JM, Thompson DC, Calligaro DO, Nelson DL, Luecke SH, Wainscott DB, Wong DT | title = Indoloxypropanolamine analogues as 5-HT(1A) receptor antagonists | journal = Bioorg. Med. Chem. Lett. | volume = 17 | issue = 20 | pages = 5600–4 | year = 2007 | pmid = 17804228 | doi = 10.1016/j.bmcl.2007.07.086 }}</ref>
| '''[[5-HT1A receptor|5-HT<sub>1A</sub>]]''' || '''15–81''' || '''Human''' || <ref name="pmid2078271">{{cite journal | vauthors = Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolaños F, Schechter L, Gozlan H | title = The main features of central 5-HT1 receptors | journal = Neuropsychopharmacology | volume = 3 | issue = 5–6 | pages = 349–360 | year = 1990 | pmid = 2078271 }}</ref><ref name="pmid1565658">{{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR | title = Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 8 | pages = 3630–3634 | date = April 1992 | pmid = 1565658 | pmc = 48922 | doi = 10.1073/pnas.89.8.3630 | doi-access = free | bibcode = 1992PNAS...89.3630W }}</ref><ref name="pmid17804228">{{cite journal | vauthors = Krushinski JH, Schaus JM, Thompson DC, Calligaro DO, Nelson DL, Luecke SH, Wainscott DB, Wong DT | title = Indoloxypropanolamine analogues as 5-HT(1A) receptor antagonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 17 | issue = 20 | pages = 5600–5604 | date = October 2007 | pmid = 17804228 | doi = 10.1016/j.bmcl.2007.07.086 }}</ref>
|-
|-
| '''[[5-HT1B receptor|5-HT<sub>1B</sub>]]''' || 4,100<br />'''34–151''' || Human<br />'''Rodent''' || <ref name="pmid1565658" /><br /><ref name="PDSP" /><ref name="pmid7984267">{{cite journal | vauthors = Boess FG, Martin IL | title = Molecular biology of 5-HT receptors | journal = Neuropharmacology | volume = 33 | issue = 3–4 | pages = 275–317 | year = 1994 | pmid = 7984267 | doi = 10.1016/0028-3908(94)90059-0| s2cid = 35553281 }}</ref>
| '''[[5-HT1B receptor|5-HT<sub>1B</sub>]]''' || 4,100<br />'''34–151''' || Human<br />'''Rodent''' || <ref name="pmid1565658" /><br /><ref name="PDSP" /><ref name="pmid7984267">{{cite journal | vauthors = Boess FG, Martin IL | title = Molecular biology of 5-HT receptors | journal = Neuropharmacology | volume = 33 | issue = 3-4 | pages = 275–317 | year = 1994 | pmid = 7984267 | doi = 10.1016/0028-3908(94)90059-0 | s2cid = 35553281 }}</ref><ref>{{cite journal | vauthors = Rojas-Corrales OM, Ortega-Alvaro A, Gibert-Rahola J, Roca-Vinardell A, Micó JA | title = Pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, enhances the analgesic effect of tramadol | journal = Pain | volume = 88 | issue = 2 | pages = 119–124 | date = November 2000 | pmid = 11050366 | doi = 10.1016/S0304-3959(00)00299-2 }}</ref>
|-
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 4,900 || Human || <ref name="pmid1565658" />
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 4,900 || Human || <ref name="pmid1565658" />
|-
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || >10,000 || Human || <ref name="pmid1513320">{{cite journal | vauthors = Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL | title = Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor | journal = Mol. Pharmacol. | volume = 42 | issue = 2 | pages = 180–5 | year = 1992 | pmid = 1513320 }}</ref>
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || >10,000 || Human || <ref name="pmid1513320">{{cite journal | vauthors = Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL | title = Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor | journal = Molecular Pharmacology | volume = 42 | issue = 2 | pages = 180–185 | date = August 1992 | pmid = 1513320 }}</ref>
|-
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || >10,000 || Human || <ref name="pmid8380639">{{cite journal | vauthors = Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA | title = Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 2 | pages = 408–12 | year = 1993 | pmid = 8380639 | pmc = 45671 | doi = 10.1073/pnas.90.2.408| bibcode = 1993PNAS...90..408A | doi-access = free }}</ref>
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || >10,000 || Human || <ref name="pmid8380639">{{cite journal | vauthors = Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA | title = Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 2 | pages = 408–412 | date = January 1993 | pmid = 8380639 | pmc = 45671 | doi = 10.1073/pnas.90.2.408 | doi-access = free | bibcode = 1993PNAS...90..408A }}</ref>
|-
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 9,333 || Human || <ref name="pmid15322733">{{cite journal | vauthors = Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M | title = Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors | journal = Naunyn Schmiedebergs Arch. Pharmacol. | volume = 370 | issue = 2 | pages = 114–23 | year = 2004 | pmid = 15322733 | doi = 10.1007/s00210-004-0951-4 | s2cid = 8938111 }}</ref>
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 9,333 || Human || <ref name="pmid15322733">{{cite journal | vauthors = Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M | title = Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 370 | issue = 2 | pages = 114–123 | date = August 2004 | pmid = 15322733 | doi = 10.1007/s00210-004-0951-4 | s2cid = 8938111 }}</ref>
|-
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 2,188 || Human || <ref name="pmid15322733" />
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 2,188 || Human || <ref name="pmid15322733" />
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| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || >10,000 || Human || <ref name="pmid15322733" />
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || >10,000 || Human || <ref name="pmid15322733" />
|-
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || ≥6,610 || Multiple || <ref name="pmid9163561">{{cite journal | vauthors = Mos J, Van Hest A, Van Drimmelen M, Herremans AH, Olivier B | title = The putative 5-HT1A receptor antagonist DU125530 blocks the discriminative stimulus of the 5-HT1A receptor agonist flesinoxan in pigeons | journal = Eur. J. Pharmacol. | volume = 325 | issue = 2–3 | pages = 145–53 | year = 1997 | pmid = 9163561 | doi = 10.1016/s0014-2999(97)00131-3}}</ref><ref name="pmid3412489">{{cite journal | vauthors = Neijt HC, Karpf A, Schoeffter P, Engel G, Hoyer D | title = Characterisation of 5-HT3 recognition sites in membranes of NG 108-15 neuroblastoma-glioma cells with [3H]ICS 205-930 | journal = Naunyn Schmiedebergs Arch. Pharmacol. | volume = 337 | issue = 5 | pages = 493–9 | year = 1988 | pmid = 3412489 | doi = 10.1007/bf00182721| s2cid = 1594844 }}</ref><ref name="pmid3352595">{{cite journal | vauthors = Hoyer D, Neijt HC | title = Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding | journal = Mol. Pharmacol. | volume = 33 | issue = 3 | pages = 303–9 | year = 1988 | pmid = 3352595 }}</ref>
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || ≥6,610 || Multiple || <ref name="pmid9163561">{{cite journal | vauthors = Mos J, Van Hest A, Van Drimmelen M, Herremans AH, Olivier B | title = The putative 5-HT1A receptor antagonist DU125530 blocks the discriminative stimulus of the 5-HT1A receptor agonist flesinoxan in pigeons | journal = European Journal of Pharmacology | volume = 325 | issue = 2–3 | pages = 145–153 | date = May 1997 | pmid = 9163561 | doi = 10.1016/s0014-2999(97)00131-3 }}</ref><ref name="pmid3412489">{{cite journal | vauthors = Neijt HC, Karpf A, Schoeffter P, Engel G, Hoyer D | title = Characterisation of 5-HT3 recognition sites in membranes of NG 108-15 neuroblastoma-glioma cells with [3H]ICS 205-930 | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 337 | issue = 5 | pages = 493–499 | date = May 1988 | pmid = 3412489 | doi = 10.1007/bf00182721 | s2cid = 1594844 }}</ref><ref name="pmid3352595">{{cite journal | vauthors = Hoyer D, Neijt HC | title = Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding | journal = Molecular Pharmacology | volume = 33 | issue = 3 | pages = 303–309 | date = March 1988 | pmid = 3352595 }}</ref>
|-
|-
|[[5-HT4 receptor|5-HT<sub>4</sub>]]
| [[5-HT5B receptor|5-HT<sub>5B</sub>]] || >1,000 || Rat || <ref name="pmid8224165">{{cite journal | vauthors = Wisden W, Parker EM, Mahle CD, Grisel DA, Nowak HP, Yocca FD, Felder CC, Seeburg PH, Voigt MM | title = Cloning and characterization of the rat 5-HT5B receptor. Evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes | journal = FEBS Lett. | volume = 333 | issue = 1–2 | pages = 25–31 | year = 1993 | pmid = 8224165 | doi = 10.1016/0014-5793(93)80368-5| doi-access = free }}</ref>
|>10,000 ?
|Rat
|<ref>{{cite journal | vauthors = Ge J, Barnes NM | title = 5-HT4 receptor-mediated modulation of 5-HT release in the rat hippocampus in vivo | journal = British Journal of Pharmacology | volume = 117 | issue = 7 | pages = 1475–1480 | date = April 1996 | pmid = 8730742 | pmc = 1909436 | doi = 10.1111/j.1476-5381.1996.tb15309.x }}</ref>
|-
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || >10,000 ({{abbr|–|(–)-Pindolol}}) || Mouse || <ref name="pmid8394987">{{cite journal | vauthors = Plassat JL, Amlaiky N, Hen R | title = Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase | journal = Mol. Pharmacol. | volume = 44 | issue = 2 | pages = 229–36 | year = 1993 | pmid = 8394987 }}</ref>
| [[5-HT5B receptor|5-HT<sub>5B</sub>]] || >1,000 || Rat || <ref name="pmid8224165">{{cite journal | vauthors = Wisden W, Parker EM, Mahle CD, Grisel DA, Nowak HP, Yocca FD, Felder CC, Seeburg PH, Voigt MM | title = Cloning and characterization of the rat 5-HT5B receptor. Evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes | journal = FEBS Letters | volume = 333 | issue = 1–2 | pages = 25–31 | date = October 1993 | pmid = 8224165 | doi = 10.1016/0014-5793(93)80368-5 | doi-access = free }}</ref>
|-
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || >10,000 || Human || <ref name="pmid8226867">{{cite journal | vauthors = Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL | title = Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase | journal = J. Biol. Chem. | volume = 268 | issue = 31 | pages = 23422–6 | year = 1993 | doi = 10.1016/S0021-9258(19)49479-9 | pmid = 8226867 | doi-access = free }}</ref><ref name="pmid9298538">{{cite journal | vauthors = Jasper JR, Kosaka A, To ZP, Chang DJ, Eglen RM | title = Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b) | journal = Br. J. Pharmacol. | volume = 122 | issue = 1 | pages = 126–32 | year = 1997 | pmid = 9298538 | pmc = 1564895 | doi = 10.1038/sj.bjp.0701336 }}</ref>
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || >10,000 ({{abbr|–|(–)-Pindolol}}) || Mouse || <ref name="pmid8394987">{{cite journal | vauthors = Plassat JL, Amlaiky N, Hen R | title = Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase | journal = Molecular Pharmacology | volume = 44 | issue = 2 | pages = 229–236 | date = August 1993 | pmid = 8394987 }}</ref>
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || >10,000 || Human || <ref name="pmid8226867">{{cite journal | vauthors = Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL | title = Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase | journal = The Journal of Biological Chemistry | volume = 268 | issue = 31 | pages = 23422–23426 | date = November 1993 | pmid = 8226867 | doi = 10.1016/S0021-9258(19)49479-9 | doi-access = free }}</ref><ref name="pmid9298538">{{cite journal | vauthors = Jasper JR, Kosaka A, To ZP, Chang DJ, Eglen RM | title = Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b) | journal = British Journal of Pharmacology | volume = 122 | issue = 1 | pages = 126–132 | date = September 1997 | pmid = 9298538 | pmc = 1564895 | doi = 10.1038/sj.bjp.0701336 }}</ref>
|-
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] || 7,585 || Pigeon || <ref name="pmid9163561"/>
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] || 7,585 || Pigeon || <ref name="pmid9163561"/>
Line 101: Line 107:
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
|-
| '''[[Beta-1 adrenergic receptor|β<sub>1</sub>]]''' || '''0.52–2.6''' || '''Human''' || <ref name="pmid17804228" /><ref name="pmid14730417">{{cite journal | vauthors = Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN | title = Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells | journal = Naunyn Schmiedebergs Arch. Pharmacol. | volume = 369 | issue = 2 | pages = 151–9 | year = 2004 | pmid = 14730417 | doi = 10.1007/s00210-003-0860-y | s2cid = 878491 }}</ref>
| '''[[Beta-1 adrenergic receptor|β<sub>1</sub>]]''' || '''0.52–2.6''' || '''Human''' || <ref name="pmid17804228" /><ref name="pmid14730417">{{cite journal | vauthors = Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN | title = Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 369 | issue = 2 | pages = 151–159 | date = February 2004 | pmid = 14730417 | doi = 10.1007/s00210-003-0860-y | s2cid = 878491 }}</ref>
|-
|-
| '''[[Beta-2 adrenergic receptor|β<sub>2</sub>]]''' || '''0.40–4.8''' || '''Human''' || <ref name="pmid17804228" /><ref name="pmid14730417" />
| '''[[Beta-2 adrenergic receptor|β<sub>2</sub>]]''' || '''0.40–4.8''' || '''Human''' || <ref name="pmid17804228" /><ref name="pmid14730417" />
|-
|-
| '''[[Beta-3 adrenergic receptor|β<sub>3</sub>]]''' || '''44''' || '''Human''' || <ref name="pmid14730417" />
| '''[[Beta-3 adrenergic receptor|β<sub>3</sub>]]''' || '''44''' || '''Human''' || <ref name="pmid14730417" /><ref>{{cite journal | vauthors = Horinouchi T, Koike K | title = (+/-)-Pindolol acts as a partial agonist at atypical beta-adrenoceptors in the guinea pig duodenum | journal = Japanese Journal of Pharmacology | volume = 85 | issue = 1 | pages = 35–40 | date = January 2001 | pmid = 11243572 | doi = 10.1254/jjp.85.35 | doi-access = free }}</ref>
|-
|-
| [[D2-like receptor|D<sub>2</sub>-like]] || >10,000 || Rat || <ref name="pmid11044891">{{cite journal | vauthors = Luedtke RR, Freeman RA, Boundy VA, Martin MW, Huang Y, Mach RH | title = Characterization of (125)I-IABN, a novel azabicyclononane benzamide selective for D2-like dopamine receptors | journal = Synapse | volume = 38 | issue = 4 | pages = 438–49 | year = 2000 | pmid = 11044891 | doi = 10.1002/1098-2396(20001215)38:4<438::AID-SYN9>3.0.CO;2-5 }}</ref>
| [[D2-like receptor|D<sub>2</sub>-like]] || >10,000 || Rat || <ref name="pmid11044891">{{cite journal | vauthors = Luedtke RR, Freeman RA, Boundy VA, Martin MW, Huang Y, Mach RH | title = Characterization of (125)I-IABN, a novel azabicyclononane benzamide selective for D2-like dopamine receptors | journal = Synapse | volume = 38 | issue = 4 | pages = 438–449 | date = December 2000 | pmid = 11044891 | doi = 10.1002/1098-2396(20001215)38:4<438::AID-SYN9>3.0.CO;2-5 | s2cid = 9578132 }}</ref>
|-
|-
| &nbsp;&nbsp;[[Dopamine D2 receptor|D<sub>2</sub>]] || >10,000 || Pigeon || <ref name="pmid9163561" />
| &nbsp;&nbsp;[[Dopamine D2 receptor|D<sub>2</sub>]] || >10,000 || Pigeon || <ref name="pmid9163561" />
|-
|-
| &nbsp;&nbsp;[[Dopamine D3 receptor|D<sub>3</sub>]] || >10,000 || Pigeon || <ref name="pmid9163561" />
| &nbsp;&nbsp;[[Dopamine D3 receptor|D<sub>3</sub>]] || >10,000 || Pigeon || <ref name="pmid9163561" />
|-
|[[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]]
|?
|?
|
|- class="sortbottom"
|- class="sortbottom"
| colspan="4" style="width: 1px;" | Values are K<sub>i</sub> (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
| colspan="4" style="width: 1px;" | Values are K<sub>i</sub> (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
|}
|}


Pindolol is a first generation,<ref>{{Cite journal|last1=Wiysonge|first1=Charles Shey|last2=Volmink|first2=Jimmy|last3=Opie|first3=Lionel H|date=2007|title=Beta-blockers and the treatment of hypertension: it is time to move on|journal=Cardiovascular Journal of Africa|volume=18|issue=6|pages=351–352|issn=1995-1892|pmc=4170499|pmid=18092107}}</ref> [[binding selectivity|non-selective]] [[beta blocker]] in the class of [[β-adrenergic receptor]] [[receptor antagonist|antagonists.]] On the receptor level it is a [[partial agonist|competitive partial agonist]]. It possesses [[Beta blocker#Intrinsic sympathomimetic activity|intrinsic sympathomimetic activity]], meaning it has some degree of agonist effects in the absence of competing ligands. Pindolol shows [[membrane-stabilizing effect]]s like [[quinidine]], possibly accounting for its antiarrhythmic effects. It also acts as a [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist]] ([[intrinsic activity]] = 20–25%) or functional [[receptor antagonist|antagonist]].<ref name="pmid16475955">{{cite journal | vauthors = Artigas F, Adell A, Celada P | title = Pindolol augmentation of antidepressant response | journal = Curr Drug Targets | volume = 7 | issue = 2 | pages = 139–47 | year = 2006 | pmid = 16475955 | doi = 10.2174/138945006775515446}}</ref>
Pindolol is a first generation,<ref>{{cite journal | vauthors = Wiysonge CS, Volmink J, Opie LH | title = Beta-blockers and the treatment of hypertension: it is time to move on | journal = Cardiovascular Journal of Africa | volume = 18 | issue = 6 | pages = 351–352 | date = 2007 | pmid = 18092107 | pmc = 4170499 }}</ref> [[binding selectivity|non-selective]] [[beta blocker]] in the class of [[β-adrenergic receptor]] [[receptor antagonist|antagonists.]] On the receptor level it is a [[partial agonist|competitive partial agonist]]. It possesses [[Beta blocker#Intrinsic sympathomimetic activity|intrinsic sympathomimetic activity]], meaning it has some degree of agonist effects in the absence of competing ligands. Pindolol shows [[membrane-stabilizing effect]]s like [[quinidine]], possibly accounting for its antiarrhythmic effects. It also acts as a [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[partial agonist]] ([[intrinsic activity]] = 20–25%) or functional [[receptor antagonist|antagonist]].<ref name="pmid16475955">{{cite journal | vauthors = Artigas F, Adell A, Celada P | title = Pindolol augmentation of antidepressant response | journal = Current Drug Targets | volume = 7 | issue = 2 | pages = 139–147 | date = February 2006 | pmid = 16475955 | doi = 10.2174/138945006775515446 }}</ref>


===Pharmacokinetics===
===Pharmacokinetics===
Line 128: Line 139:


===Depression===
===Depression===
Pindolol has been investigated as an [[adjunct therapy|add-on drug]] to [[antidepressant]] therapy with SSRIs like [[fluoxetine]] in the treatment of [[depression (mood)|depression]] since 1994.<ref>Pérez, V., Gilaberte, I., Faries, D., Alvarez, E. and Artigas, F., 1997. Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment. The Lancet, 349(9065), pp.1594-1597.
Pindolol has been investigated as an [[adjunct therapy|add-on drug]] to [[antidepressant]] therapy with SSRIs like [[fluoxetine]] in the treatment of [[depression (mood)|depression]] since 1994.<ref name="pmid25689398" /> The rationale behind this strategy has its basis in the fact that pindolol is an antagonist of the serotonin 5-HT<sub>1A</sub> receptor.<ref name="pmid23757185">{{cite journal | vauthors = Celada P, Bortolozzi A, Artigas F | title = Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research | journal = CNS Drugs | volume = 27 | issue = 9 | pages = 703–16 | year = 2013 | pmid = 23757185 | doi = 10.1007/s40263-013-0071-0 | s2cid = 31931009 }}</ref> [[Presynaptic]] and [[somatodendritic]] 5-HT<sub>1A</sub> receptors act as [[inhibitory postsynaptic potential|inhibitory]] [[autoreceptor]]s, inhibit [[serotonin]] [[neurotransmitter release|release]], and are pro-depressive in their action.<ref name="pmid23757185" /> This is in contrast to postsynaptic 5-HT<sub>1A</sub> receptors, which mediate antidepressant effects.<ref name="pmid23757185" /> By blocking 5-HT<sub>1A</sub> autoreceptors at doses that are [[binding selectivity|selective]] for them over postsynaptic 5-HT<sub>1A</sub> receptors, pindolol may be able to disinhibit serotonin release and thereby improve the antidepressant effects of SSRIs.<ref name="pmid23757185" /> The results of augmentation therapy with pindolol have been encouraging in early studies of low quality.<ref name="pmid9635544">{{cite journal | vauthors = Blier P, Bergeron R | title = The use of pindolol to potentiate antidepressant medication | journal = J Clin Psychiatry | volume = 59 Suppl 5 | pages = 16–23; discussion 24–5 | year = 1998 | pmid = 9635544 }}</ref> A 2015 [[systematic review]] and [[meta-analysis]] of five [[randomized controlled trial]]s found no overall significant benefit at 2.5&nbsp;mg although, with regard to patients with SSRI-resistant depression, "once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients".<ref name="pmid25689398">{{cite journal | vauthors = Liu Y, Zhou X, Zhu D, Chen J, Qin B, Zhang Y, Wang X, Yang D, Meng H, Luo Q, Xie P | title = Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis | journal = Hum Psychopharmacol | volume = 30 | issue = 3 | pages = 132–42 | year = 2015 | pmid = 25689398 | doi = 10.1002/hup.2465 | s2cid = 205925716 }}</ref> On the other hand, a 2017 systematic review indicated that pindolol's efficacy has been demonstrated in high evidence studies.<ref name="Kleeblatt">{{Cite journal |last=Kleeblatt |first=Julia |last2=Betzler |first2=Felix |last3=Kilarski |first3=Laura L. |last4=Bschor |first4=Tom |last5=Köhler |first5=Stephan |date=2017 |title=Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence |url=https://linkinghub.elsevier.com/retrieve/pii/S0924977X17301852 |journal=European Neuropsychopharmacology |language=en |volume=27 |issue=5 |pages=423–441 |doi=10.1016/j.euroneuro.2017.03.003}}</ref>Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact.<ref name="pmid23757185" /><ref name="Kleeblatt" /> Pindolol's antidepressive efficacy may predominently result from its ability to desensitize 5-HT<sub>1A</sub> autoreceptors.<ref>{{cite journal |last1=Haddjeri |first1=N |last2=Blier |first2=P |title=Effects of sustained (+/-)pindolol administration on serotonin neurotransmission in rats |journal=J Psychiatry Neurosci. |date=2000 |volume=25 |issue=4 |pages=378-88 |pmid=11022403 |url=https://pubmed.ncbi.nlm.nih.gov/11022403/ |access-date=13 August 2022}}</ref>
</ref><ref name="pmid25689398" /> The rationale behind this strategy has its basis in the fact that pindolol is an antagonist of the serotonin 5-HT<sub>1A</sub> receptor.<ref name="pmid23757185">{{cite journal | vauthors = Celada P, Bortolozzi A, Artigas F | title = Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research | journal = CNS Drugs | volume = 27 | issue = 9 | pages = 703–716 | date = September 2013 | pmid = 23757185 | doi = 10.1007/s40263-013-0071-0 | s2cid = 31931009 }}</ref> [[Presynaptic]] and [[somatodendritic]] 5-HT<sub>1A</sub> receptors act as [[inhibitory postsynaptic potential|inhibitory]] [[autoreceptor]]s, inhibit [[serotonin]] [[neurotransmitter release|release]], and are pro-depressive in their action.<ref name="pmid23757185" /> This is in contrast to postsynaptic 5-HT<sub>1A</sub> receptors, which mediate antidepressant effects.<ref name="pmid23757185" /> By blocking 5-HT<sub>1A</sub> autoreceptors at doses that are [[binding selectivity|selective]] for them over postsynaptic 5-HT<sub>1A</sub> receptors, pindolol may be able to disinhibit serotonin release and thereby improve the antidepressant effects of SSRIs.<ref name="pmid23757185" /> The results of augmentation therapy with pindolol have been encouraging in early studies of low quality.<ref name="pmid9635544">{{cite journal | vauthors = Blier P, Bergeron R | title = The use of pindolol to potentiate antidepressant medication | journal = The Journal of Clinical Psychiatry | volume = 59 | issue = Suppl 5 | pages = 16–23; discussion 24–5 | year = 1998 | pmid = 9635544 }}</ref> A 2015 [[systematic review]] and [[meta-analysis]] of five [[randomized controlled trial]]s found no overall significant benefit at 2.5&nbsp;mg although, with regard to patients with SSRI-resistant depression, "once-daily high-dose pindolol (7.5&nbsp;mg qd) appears to show a promising benefit in these patients".<ref name="pmid25689398">{{cite journal | vauthors = Liu Y, Zhou X, Zhu D, Chen J, Qin B, Zhang Y, Wang X, Yang D, Meng H, Luo Q, Xie P | title = Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis | journal = Human Psychopharmacology | volume = 30 | issue = 3 | pages = 132–142 | date = May 2015 | pmid = 25689398 | doi = 10.1002/hup.2465 | s2cid = 205925716 }}</ref> On the other hand, a 2017 systematic review indicated that pindolol's efficacy has been demonstrated in high evidence studies.<ref name="Kleeblatt">{{cite journal | vauthors = Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S | title = Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence | journal = European Neuropsychopharmacology | volume = 27 | issue = 5 | pages = 423–441 | date = May 2017 | pmid = 28318897 | doi = 10.1016/j.euroneuro.2017.03.003 | s2cid = 3740987 }}</ref> Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact.<ref name="pmid23757185" /><ref name="Kleeblatt" /> Pindolol's antidepressive efficacy may predominantly result from its ability to desensitize 5-HT<sub>1A</sub> autoreceptors.<ref>{{cite journal | vauthors = Haddjeri N, Blier P | title = Effects of sustained (+/-)pindolol administration on serotonin neurotransmission in rats | journal = Journal of Psychiatry & Neuroscience | volume = 25 | issue = 4 | pages = 378–388 | date = September 2000 | pmid = 11022403 | pmc = 1407726 }}</ref>


===Others===
===Others===
* Pindolol is a potent scavenger of [[nitric oxide]]. This effect is potentiated by [[sodium bicarbonate]]. Inhibition of nitric oxide synthesis has an anxiolytic effect in animals.<ref>{{cite journal | doi=10.1016/j.lfs.2005.02.018 | volume=77 | issue=16 | title=Pindolol is a potent scavenger of reactive nitrogen species | journal=Life Sciences | pages=1983–1992 | pmid=15916777 | last1 = Fernandes | first1 = E | last2 = Gomes | first2 = A | last3 = Costa | first3 = D | last4 = Lima | first4 = JL| year=2005 }}</ref>
* Pindolol is a potent scavenger of [[nitric oxide]]. This effect is potentiated by [[sodium bicarbonate]]. Inhibition of nitric oxide synthesis has an anxiolytic effect in animals.<ref>{{cite journal | vauthors = Fernandes E, Gomes A, Costa D, Lima JL | title = Pindolol is a potent scavenger of reactive nitrogen species | journal = Life Sciences | volume = 77 | issue = 16 | pages = 1983–1992 | date = September 2005 | pmid = 15916777 | doi = 10.1016/j.lfs.2005.02.018 }}</ref>
* Augmentation therapy of [[premature ejaculation]]: According to a recent study, pindolol can be effectively added to a standard anti-premature-ejaculation therapy, which usually consists of daily doses of an SSRI antidepressant such as fluoxetine or paroxetine. Augmentation of pindolol results in substantial increase of ejaculatory latency, even in those who previously did not experience in an improvement with the SSRI monotherapy.<ref>{{cite journal | last1 = Safarinejad | first1 = MR | title = Once-daily high-dose pindolol for paroxetine-refractory premature ejaculation: a double-blind, placebo-controlled and randomized study. | journal = Journal of Clinical Psychopharmacology | volume = 28 | issue = 1 | pages = 39–44 | year = 2008 | pmid = 18204339 | doi = 10.1097/jcp.0b013e31816073a5| s2cid = 9936458 }}</ref>
* Augmentation therapy of [[premature ejaculation]]: According to a recent study, pindolol can be effectively added to a standard anti-premature-ejaculation therapy, which usually consists of daily doses of an SSRI antidepressant such as fluoxetine or paroxetine. Augmentation of pindolol results in substantial increase of ejaculatory latency, even in those who previously did not experience in an improvement with the SSRI monotherapy.<ref>{{cite journal | vauthors = Safarinejad MR | title = Once-daily high-dose pindolol for paroxetine-refractory premature ejaculation: a double-blind, placebo-controlled and randomized study | journal = Journal of Clinical Psychopharmacology | volume = 28 | issue = 1 | pages = 39–44 | date = February 2008 | pmid = 18204339 | doi = 10.1097/jcp.0b013e31816073a5 | s2cid = 9936458 }}{{Retracted|doi=10.1097/JCP.0000000000001540|pmid=35230053|https://retractionwatch.com/?s=Mohammad+Reza+Safarinejad ''Retraction Watch''}}</ref>


==See also==
== See also ==
* [[Bopindolol]]
* [[Bopindolol]]


==References==
== References ==
{{Reflist|2}}
{{Reflist|2}}


Latest revision as of 09:32, 25 June 2024

Pindolol
Skeletal formula of pindolol
Space-filling model of the pindolol molecule
Clinical data
Trade namesVisken, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa684032
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability50% to 95%
MetabolismHepatic
Elimination half-life3–4 hours
ExcretionRenal
Identifiers
  • (RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.033.501 Edit this at Wikidata
Chemical and physical data
FormulaC14H20N2O2
Molar mass248.326 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • CC(C)NCC(O)COc2cccc1[nH]ccc12
  • InChI=1S/C14H20N2O2/c1-10(2)16-8-11(17)9-18-14-5-3-4-13-12(14)6-7-15-13/h3-7,10-11,15-17H,8-9H2,1-2H3 ☒N
  • Key:JZQKKSLKJUAGIC-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension.[1][2] It is also an antagonist of the serotonin 5-HT1A receptor, preferentially blocking inhibitory 5-HT1A autoreceptors, and has been researched as an add-on therapy to various antidepressants, such as clomipramine and the selective serotonin reuptake inhibitors (SSRIs), in the treatment of depression[3][4][5] and obsessive-compulsive disorder.[6][7]

Medical uses

[edit]

Pindolol is used for hypertension in the United States, Canada, and Europe, and also for angina pectoris outside the United States.[2] When used alone for hypertension, pindolol can significantly lower blood pressure and heart rate, but the evidence base for its use is weak as the number of subjects in published studies is small.[2] In some countries, pindolol is also used for arrhythmias and prophylaxis of acute stress reactions.[medical citation needed]

Contraindications

[edit]
See also: Beta blocker § Contraindications, and Propranolol § Contraindications

Similar to propranolol with an extra contraindication for hyperthyroidism. In patients with thyrotoxicosis, possible deleterious effects from long-term use of pindolol have not been adequately appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or complications, and give a false impression of improvement. Therefore, abrupt withdrawal of pindolol may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.[8]

Pindolol has intrinsic sympathomimetic activity and is therefore used with caution in angina pectoris.[8]

Pharmacology

[edit]

Pharmacodynamics

[edit]
Pindolol[9]
Site Ki (nM) Species Ref
5-HT1A 15–81 Human [10][11][12]
5-HT1B 4,100
34–151		 Human
Rodent		 [11]
[9][13][14]
5-HT1D 4,900 Human [11]
5-HT1E >10,000 Human [15]
5-HT1F >10,000 Human [16]
5-HT2A 9,333 Human [17]
5-HT2B 2,188 Human [17]
5-HT2C >10,000 Human [17]
5-HT3 ≥6,610 Multiple [18][19][20]
5-HT4 >10,000 ? Rat [21]
5-HT5B >1,000 Rat [22]
5-HT6 >10,000 (–) Mouse [23]
5-HT7 >10,000 Human [24][25]
α1 7,585 Pigeon [18]
α2 ND ND ND
β1 0.52–2.6 Human [12][26]
β2 0.40–4.8 Human [12][26]
β3 44 Human [26][27]
D2-like >10,000 Rat [28]
  D2 >10,000 Pigeon [18]
  D3 >10,000 Pigeon [18]
M1 ? ?
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Pindolol is a first generation,[29] non-selective beta blocker in the class of β-adrenergic receptor antagonists. On the receptor level it is a competitive partial agonist. It possesses intrinsic sympathomimetic activity, meaning it has some degree of agonist effects in the absence of competing ligands. Pindolol shows membrane-stabilizing effects like quinidine, possibly accounting for its antiarrhythmic effects. It also acts as a serotonin 5-HT1A receptor partial agonist (intrinsic activity = 20–25%) or functional antagonist.[30]

Pharmacokinetics

[edit]

Pindolol is rapidly and well absorbed from the GI tract. It undergoes some first-pass-metabolization leading to an oral bioavailability of 50-95%. Patients with uremia may have a reduced bioavailability. Food does not alter the bioavailability, but may increase the resorption. Following an oral single dose of 20 mg peak plasma concentrations are reached within 1–2 hours. The effect of pindolol on pulse rate (lowering) is evident after 3 hours. Despite the rather short halflife of 3–4 hours, hemodynamic effects persist for 24 hours after administration. Plasma halflives are increased to 3–11.5 hours in patients with renal impairment, to 7–15 hours in elderly patients, and from 2.5 to 30 hours in patients with liver cirrhosis. Approximately 2/3 of pindolol is metabolized in the liver giving hydroxylates, which are found in the urine as gluconurides and ethereal sulfates. The remaining 1/3 of pindolol is excreted in urine in unchanged form.

History

[edit]

Pindolol was patented by Sandoz in 1969 and was launched in the US in 1977.[31] Towards end of February 2020 FDA added this product to their "DRUG SHORTAGE" list stating this is due to "Shortage of an active ingredient" and this is likely to be related to Coronavirus outbreak and related supply chain impacts.

Research

[edit]

Depression

[edit]

Pindolol has been investigated as an add-on drug to antidepressant therapy with SSRIs like fluoxetine in the treatment of depression since 1994.[32][5] The rationale behind this strategy has its basis in the fact that pindolol is an antagonist of the serotonin 5-HT1A receptor.[4] Presynaptic and somatodendritic 5-HT1A receptors act as inhibitory autoreceptors, inhibit serotonin release, and are pro-depressive in their action.[4] This is in contrast to postsynaptic 5-HT1A receptors, which mediate antidepressant effects.[4] By blocking 5-HT1A autoreceptors at doses that are selective for them over postsynaptic 5-HT1A receptors, pindolol may be able to disinhibit serotonin release and thereby improve the antidepressant effects of SSRIs.[4] The results of augmentation therapy with pindolol have been encouraging in early studies of low quality.[3] A 2015 systematic review and meta-analysis of five randomized controlled trials found no overall significant benefit at 2.5 mg although, with regard to patients with SSRI-resistant depression, "once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients".[5] On the other hand, a 2017 systematic review indicated that pindolol's efficacy has been demonstrated in high evidence studies.[33] Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact.[4][33] Pindolol's antidepressive efficacy may predominantly result from its ability to desensitize 5-HT1A autoreceptors.[34]

Others

[edit]
  • Pindolol is a potent scavenger of nitric oxide. This effect is potentiated by sodium bicarbonate. Inhibition of nitric oxide synthesis has an anxiolytic effect in animals.[35]
  • Augmentation therapy of premature ejaculation: According to a recent study, pindolol can be effectively added to a standard anti-premature-ejaculation therapy, which usually consists of daily doses of an SSRI antidepressant such as fluoxetine or paroxetine. Augmentation of pindolol results in substantial increase of ejaculatory latency, even in those who previously did not experience in an improvement with the SSRI monotherapy.[36]

See also

[edit]

References

[edit]
  1. ^ a b Drugs.com International brand names for pindolol Archived 2017-10-01 at the Wayback Machine Page accessed Sept 4, 2015
  2. ^ a b c Wong GW, Boyda HN, Wright JM (November 2014). "Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension". The Cochrane Database of Systematic Reviews. 2014 (11): CD007450. doi:10.1002/14651858.CD007450.pub2. PMC 6486122. PMID 25427719.
  3. ^ a b Blier P, Bergeron R (1998). "The use of pindolol to potentiate antidepressant medication". The Journal of Clinical Psychiatry. 59 (Suppl 5): 16–23, discussion 24–5. PMID 9635544.
  4. ^ a b c d e f Celada P, Bortolozzi A, Artigas F (September 2013). "Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research". CNS Drugs. 27 (9): 703–716. doi:10.1007/s40263-013-0071-0. PMID 23757185. S2CID 31931009.
  5. ^ a b c Liu Y, Zhou X, Zhu D, Chen J, Qin B, Zhang Y, et al. (May 2015). "Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis". Human Psychopharmacology. 30 (3): 132–142. doi:10.1002/hup.2465. PMID 25689398. S2CID 205925716.
  6. ^ Mundo, Emanuela, Emanuela Guglielmo, and Laura Bellodi. "Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double blind, placedo-controlled study." International clinical psychopharmacology 13, no. 5 (1998): 219-224.
  7. ^ Sassano-Higgins, S.A. and Pato, M.T., 2015. Pindolol augmentation of selective serotonin reuptake inhibitors and clomipramine for the treatment of obsessive-compulsive disorder: A meta-analysis. Journal of Pharmacology and Pharmacotherapeutics, 6(1), pp.36-38.
  8. ^ a b "RxMed: Pharmaceutical Information - VISKEN". Archived from the original on 2011-09-27. Retrieved 2010-08-15.
  9. ^ a b Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  10. ^ Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolaños F, et al. (1990). "The main features of central 5-HT1 receptors". Neuropsychopharmacology. 3 (5–6): 349–360. PMID 2078271.
  11. ^ a b c Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR (April 1992). "Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta". Proceedings of the National Academy of Sciences of the United States of America. 89 (8): 3630–3634. Bibcode:1992PNAS...89.3630W. doi:10.1073/pnas.89.8.3630. PMC 48922. PMID 1565658.
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