Pindolol

Pindolol

Systematic (IUPAC) name
(RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
Clinical data
Trade names	Visken (originator), many generic brands
AHFS/Drugs.com	monograph
MedlinePlus	a684032
Pregnancy category	AU: C US: B (No risk in non-human studies)
Legal status	℞ (Prescription only)
Routes of administration	oral, iv
Pharmacokinetic data
Bioavailability	50% to 95%
Metabolism	Hepatic
Biological half-life	3–4 hours
Excretion	Renal
Identifiers
CAS Number	13523-86-9 Y
ATC code	C07AA03 (WHO)
PubChem	CID: 4828
IUPHAR/BPS	91
DrugBank	DB00960 N
ChemSpider	4662 N
UNII	BJ4HF6IU1D N
KEGG	D00513 Y
ChEBI	CHEBI:8214 N
ChEMBL	CHEMBL500 N
Chemical data
Formula	C14H20N2O2
Molecular mass	248.321 g/mol
SMILES CC(C)NCC(O)COc2cccc1nccc12
InChI 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
NY (what is this?)  (verify)

Pindolol (originally marketed as Visken, now marketed under many brands as a generic drug) is a beta blocker.

Medical use

Pindolol is used for hypertension in the US, Canada, and Europe, and also for angina pectoris outside the US. 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.

In some countries pindolol is also used for arrhythmias and prophylaxis of acute stress reactions.

Contraindications

See also: Propranolol

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.

Pindolol has modest beta-adrenergic agonist activity and is therefore used with caution in angina pectoris.

Pharmacology

Pindolol is a nonselective beta blocker with partial beta-adrenergic receptor agonist activity and also possesses intrinsic sympathomimetic activity. This means that pindolol, particularly in high doses, exerts effects like epinephrine or isoprenaline (increased pulse rate, increased blood pressure, bronchodilation), but these effects are limited. Pindolol also shows membrane stabilizing effects like quinidine, possibly accounting for its antiarrhythmic effects. It also functions as a 5-HT_1A receptor weak partial agonist / antagonist (K_i=33nM).

Pharmacokinetics

Pindolol is rapidly and well absorbed from the GI tract. It undergoes some first-pass-metabolization leading to an oral bioavailability of 50 to 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 to 2 hours. The effect of pindolol on pulse rate (lowering) is evident after 3 hours. Despite the rather short halflife of 3 to 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 are 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 1966 and was launched in the US in 1977.

Research

• Augmentation therapy of clinical depression: Pindolol is sometimes added to a standard antidepressant therapy, if the patient fails to respond to the standard therapy alone. Fluoxetine is the most commonly used standard antidepressant. The results of augmentation therapy are encouraging. It is not known whether pindolol has antidepressive activities as monotherapeutic agent.
• Pindolol is a potent scavenger of nitric oxide. This affect is potentiated by sodium bicarbonate. Inhibition of nitric oxide synthesis has an anxiolytic effect in animals.
• 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.