Pindolol

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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
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

obsessive-compulsive disorder.[6][7]

Medical uses

Pindolol is used for

stress reactions.[medical citation needed
]

Contraindications

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

angina pectoris.[8]

Pharmacology

Pharmacodynamics

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,

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

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

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

Depression

Pindolol has been investigated as an

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

  • 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

References

  1. ^ a b Drugs.com International brand names for pindolol Archived 2017-10-01 at the Wayback Machine Page accessed Sept 4, 2015
  2. ^
    PMID 25427719
    .
  3. ^
    PMID 9635544
    .
  4. ^
    S2CID 31931009
    .
  5. ^
    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. PMID 2078271
    .
  11. ^
    PMID 1565658
    .
  12. ^
    PMID 17804228
    .
  13. S2CID 35553281
    .
  14. PMID 11050366
    .
  15. PMID 1513320
    .
  16. PMID 8380639
    .
  17. ^
    S2CID 8938111
    .
  18. ^
    PMID 9163561
    .
  19. S2CID 1594844
    .
  20. PMID 3352595
    .
  21. PMID 8730742
    .
  22. PMID 8224165
    .
  23. PMID 8394987
    .
  24. PMID 8226867
    .
  25. PMID 9298538
    .
  26. ^
    S2CID 878491
    .
  27. PMID 11243572
    .
  28. S2CID 9578132
    .
  29. PMID 18092107
    .
  30. PMID 16475955
    .
  31. ISBN 9780941901215 p 185
  32. ^ 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.
  33. ^
    S2CID 3740987
    .
  34. PMID 11022403
    .
  35. PMID 15916777
    .
  36. S2CID 9936458
    .
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