Pindolol: Difference between revisions

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{{cs1 config|name-list-style=vanc|display-authors=6}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = verified
| verifiedrevid = 408558126
| verifiedrevid = 408558126
| IUPAC_name = (''RS'')-1-(1''H''-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
| image = Pindolol skeletal.svg
| image = Pindolol skeletal.svg
| alt = Skeletal formula of pindolol
| alt = Skeletal formula of pindolol
Line 11: Line 10:
| alt2 = Space-filling model of the pindolol molecule
| alt2 = Space-filling model of the pindolol molecule
| width2 = 225px
| width2 = 225px
| chirality = [[Racemic mixture]]
 
<!--Clinical data-->
<!-- Clinical data -->
| tradename = Visken, others<ref name="Drugs.com" />
| tradename = Visken, others<ref name="Drugs.com" />
| Drugs.com = {{drugs.com|monograph|pindolol}}
| Drugs.com = {{drugs.com|monograph|pindolol}}
Line 21: Line 20:
| legal_status = Rx-only
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|By mouth]], [[intravenous therapy|intravenous]]
| routes_of_administration = [[Oral administration|By mouth]], [[intravenous therapy|intravenous]]
<!--Pharmacokinetic data-->
| class = [[Beta blocker]]; [[β-Adrenergic receptor]] [[receptor antagonist|antagonist]]; [[Binding selectivity|Non-selective]] [[beta-1 adrenergic receptor|β<sub>1</sub>-]] and [[beta-2 adrenergic receptor|β<sub>2</sub>-adrenergic receptor]] [[receptor antagonist]]
| ATC_prefix = C07
| ATC_suffix = AA03
 
<!-- Pharmacokinetic data -->
| bioavailability = 50% to 95%
| bioavailability = 50% to 95%
| protein_bound =
| metabolism = [[Liver|Hepatic]]
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 3&ndash;4 hours
| metabolites =
| elimination_half-life = 3–4 hours
| excretion = [[Kidney|Renal]]
| excretion = [[Kidney|Renal]]
<!--Identifiers-->
 
| CAS_number_Ref = {{cascite|correct|??}}
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 13523-86-9
| CAS_number = 13523-86-9
| ATC_prefix = C07
| ATC_suffix = AA03
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 8214
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = JZQKKSLKJUAGIC-UHFFFAOYSA-N
| PubChem = 4828
| PubChem = 4828
| IUPHAR_ligand = 91
| IUPHAR_ligand = 91
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00960
| DrugBank = DB00960
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4662
| ChemSpiderID = 4662
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BJ4HF6IU1D
| UNII = BJ4HF6IU1D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00513
| KEGG = D00513
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8214
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 500
| ChEMBL = 500
<!--Chemical data-->
| synonyms =
 
<!-- Chemical data -->
| IUPAC_name = (''RS'')-1-(1''H''-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
| C=14 | H=20 | N=2 | O=2
| C=14 | H=20 | N=2 | O=2
| chirality = [[Racemic mixture]]
| SMILES = CC(C)NCC(O)COc2cccc1[nH]ccc12
| SMILES = CC(C)NCC(O)COc2cccc1[nH]ccc12
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = JZQKKSLKJUAGIC-UHFFFAOYSA-N
}}
}}


'''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>
'''Pindolol''', sold under the brand name '''Visken''' among others, is a [[binding selectivity|non-selective]] [[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]] (OCD).<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==
Pindolol is used for [[hypertension]] in the [[United States]], [[Canada]], and [[Europe]], and also for [[angina pectoris]] outside the United States.<ref name="Cochrane" /> 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.<ref name=Cochrane/> In some countries, pindolol is also used for [[arrhythmias]] and [[prophylaxis]] of acute [[stress (medicine)|stress]] reactions.{{Medical citation needed|date=September 2015}}
Pindolol is used for [[hypertension]] in the [[United States]], [[Canada]], and [[Europe]], and also for [[angina pectoris]] outside the United States.<ref name="Cochrane" /> 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.<ref name=Cochrane/> In some countries, pindolol is also used for [[arrhythmias]] and [[prophylaxis]] of acute [[stress (medicine)|stress]] reactions.{{Medical citation needed|date=September 2015}} It has been used to treat [[anxiety]] as well.<ref name="BoyceBalloneCerta2021">{{cite journal | vauthors = Boyce TG, Ballone NT, Certa KM, Becker MA | title = The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review | journal = J Acad Consult Liaison Psychiatry | volume = 62 | issue = 4 | pages = 404–412 | date = 2021 | pmid = 34210401 | doi = 10.1016/j.jaclp.2020.12.009 | url = }}</ref><ref name="ArcherWilesKessler2025">{{cite journal | vauthors = Archer C, Wiles N, Kessler D, Turner K, Caldwell DM | title = Beta-blockers for the treatment of anxiety disorders: A systematic review and meta-analysis | journal = J Affect Disord | volume = 368 | issue = | pages = 90–99 | date = January 2025 | pmid = 39271062 | doi = 10.1016/j.jad.2024.09.068 | url = | doi-access = free }}</ref>


==Contraindications==
==Contraindications==
Line 67: Line 75:


==Pharmacology==
==Pharmacology==
===Pharmacodynamics===
===Pharmacodynamics===
{| class="wikitable floatleft" style="font-size:small;"
{| class="wikitable floatleft" style="font-size:small;"
Line 74: Line 81:
! 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 = 349–360 | 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-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><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-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" />
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| [[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-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-HT4 receptor|5-HT<sub>4</sub>]]
|>10,000 ?
| >10,000 ?
|Rat
| 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>
| <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-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-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>
Line 107: Line 114:
| [[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-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-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" /><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>
| [[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 = 438–449 | date = December 2000 | pmid = 11044891 | doi = 10.1002/1098-2396(20001215)38:4<438::AID-SYN9>3.0.CO;2-5 | s2cid = 9578132 }}</ref>
| [[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>
Line 119: Line 126:
| &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>]]
| [[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.
Line 131: Line 138:
===Pharmacokinetics===
===Pharmacokinetics===
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&nbsp;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.
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&nbsp;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.
==Chemistry==
The experimental [[log P]] of pindolol is 1.75 to 1.9.<ref name="PubChem">https://pubchem.ncbi.nlm.nih.gov/compound/4828</ref><ref name="DrugBank">https://go.drugbank.com/drugs/DB00960</ref>


==History==
==History==
Line 137: Line 147:


==Research==
==Research==
===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>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.
Line 145: Line 154:
* 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>
* 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>


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


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


{{Beta blockers}}
{{Beta blockers}}
{{Anxiolytics}}
{{Adrenergic receptor modulators}}
{{Adrenergic receptor modulators}}
{{Serotonin receptor modulators}}
{{Serotonin receptor modulators}}


[[Category:Indoles]]
[[Category:5-HT1A antagonists]]
[[Category:5-HT1A antagonists]]
[[Category:Antidepressants]]
[[Category:Antidepressants]]
[[Category:Antihypertensive agents]]
[[Category:Antihypertensive agents]]
[[Category:Anxiolytics]]
[[Category:Beta blockers]]
[[Category:Beta blockers]]
[[Category:Indole ethers at the benzene ring]]
[[Category:Indole ethers at the benzene ring]]
[[Category:Indoles]]
[[Category:N-isopropyl-phenoxypropanolamines]]
[[Category:N-isopropyl-phenoxypropanolamines]]

Latest revision as of 06:46, 30 June 2025

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| _other_data=(RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol

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Pindolol, sold under the brand name Visken among others, is a non-selective 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 (OCD).[6][7]

Medical uses

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.Template:Medical citation needed It has been used to treat anxiety as well.[8][9]

Contraindications

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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.[10]

Pindolol has intrinsic sympathomimetic activity and is therefore used with caution in angina pectoris.[10]

Pharmacology

Pharmacodynamics

Pindolol[11]
Site Ki (nM) Species Ref
5-HT1A 15–81 Human [12][13][14]
5-HT1B 4,100
34–151		 Human
Rodent		 [13]
[11][15][16]
5-HT1D 4,900 Human [13]
5-HT1E >10,000 Human [17]
5-HT1F >10,000 Human [18]
5-HT2A 9,333 Human [19]
5-HT2B 2,188 Human [19]
5-HT2C >10,000 Human [19]
5-HT3 ≥6,610 Multiple [20][21][22]
5-HT4 >10,000 ? Rat [23]
5-HT5B >1,000 Rat [24]
5-HT6 >10,000 (–) Mouse [25]
5-HT7 >10,000 Human [26][27]
α1 7,585 Pigeon [20]
α2 ND ND ND
β1 0.52–2.6 Human [14][28]
β2 0.40–4.8 Human [14][28]
β3 44 Human [28][29]
D2-like >10,000 Rat [30]
  D2 >10,000 Pigeon [20]
  D3 >10,000 Pigeon [20]
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,[31] 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.[32] The drug additionally shows affinity for the serotonin 5-HT1B receptor.[33]

Pharmacokinetics

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.

Chemistry

The experimental log P of pindolol is 1.75 to 1.9.[34][35]

History

Pindolol was patented by Sandoz in 1969 and was launched in the US in 1977.[36] 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

Depression

Pindolol has been investigated as an add-on drug to antidepressant therapy with SSRIs like fluoxetine in the treatment of depression since 1994.[37][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 and clomipramine.[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.[38] Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact.[4][38] Pindolol's antidepressive efficacy may predominantly result from its ability to desensitize 5-HT1A autoreceptors.[39]

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.[40]

See also

References

Template:Reflist

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  1. ↑ a b Drugs.com International brand names for pindolol Template:Webarchive Page accessed Sept 4, 2015
  2. ↑ a b c Script error: No such module "Citation/CS1".
  3. ↑ a b Script error: No such module "Citation/CS1".
  4. ↑ a b c d e f Script error: No such module "Citation/CS1".
  5. ↑ a b c Script error: No such module "Citation/CS1".
  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. ↑ Script error: No such module "Citation/CS1".
  9. ↑ Script error: No such module "Citation/CS1".
  10. ↑ a b Script error: No such module "citation/CS1".
  11. ↑ a b Script error: No such module "citation/CS1".
  12. ↑ Script error: No such module "Citation/CS1".
  13. ↑ a b c Script error: No such module "Citation/CS1".
  14. ↑ a b c Script error: No such module "Citation/CS1".
  15. ↑ Script error: No such module "Citation/CS1".
  16. ↑ Script error: No such module "Citation/CS1".
  17. ↑ Script error: No such module "Citation/CS1".
  18. ↑ Script error: No such module "Citation/CS1".
  19. ↑ a b c Script error: No such module "Citation/CS1".
  20. ↑ a b c d Script error: No such module "Citation/CS1".
  21. ↑ Script error: No such module "Citation/CS1".
  22. ↑ Script error: No such module "Citation/CS1".
  23. ↑ Script error: No such module "Citation/CS1".
  24. ↑ Script error: No such module "Citation/CS1".
  25. ↑ Script error: No such module "Citation/CS1".
  26. ↑ Script error: No such module "Citation/CS1".
  27. ↑ Script error: No such module "Citation/CS1".
  28. ↑ a b c Script error: No such module "Citation/CS1".
  29. ↑ Script error: No such module "Citation/CS1".
  30. ↑ Script error: No such module "Citation/CS1".
  31. ↑ Script error: No such module "Citation/CS1".
  32. ↑ Script error: No such module "Citation/CS1".
  33. ↑ Script error: No such module "Citation/CS1".
  34. ↑ https://pubchem.ncbi.nlm.nih.gov/compound/4828
  35. ↑ https://go.drugbank.com/drugs/DB00960
  36. ↑ "Discovery and Development of Major Drugs. Chapter 2 in Pharmaceutical Innovation: Revolutionizing Human Health. Volume 2 of Chemical Heritage Foundation series in innovation and entrepreneurship. Eds Ralph Landau, Basil Achilladelis, Alexander Scriabine. Chemical Heritage Foundation, 1999. Template:ISBN p 185
  37. ↑ 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.
  38. ↑ a b Script error: No such module "Citation/CS1".
  39. ↑ Script error: No such module "Citation/CS1".
  40. ↑ Script error: No such module "Citation/CS1".
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