Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

.Drugs.co
International brand names for pindolol
Page accessed Sept 4, 2015 It is also an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of the

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

5-HT_1A receptor, preferentially blocking

inhibitory An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a Chemical synapse, postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Inc ...

5-HT_1A autoreceptors, and has been researched as an add-on therapy to selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression.

Medical uses

Pindolol is used for

in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

, and

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

, and also for angina pectoris outside the United States. When used alone for hypertension, pindolol can significantly lower

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

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

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 intrinsic sympathomimetic activity and is therefore used with caution in angina pectoris.

Pharmacology

Pharmacodynamics

Pindolol is a first generation,

non-selective In biochemistry and pharmacology, a ligand is a Chemical substance, substance that forms a Complex (chemistry), complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-lig ...

beta blocker in the class of

β-adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

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 effect Membrane stabilizing effects involve the inhibition or total abolishing of action potentials from being propagated across the membrane. This phenomenon is common in nerve tissues as they are the carrier of impulses from the periphery to the central ...

s like quinidine, possibly accounting for its antiarrhythmic effects. It also acts as a

5-HT_1A receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

( intrinsic activity = 20–25%) or functional

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. 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 Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

therapy with SSRIs like

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

in the treatment of depression since 1994. The rationale behind this strategy has its basis in the fact that pindolol is an antagonist of the serotonin 5-HT_1A receptor. Presynaptic and

somatodendritic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

5-HT_1A receptors act as

autoreceptors, inhibit

release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to ident ...

, and are pro-depressive in their action. This is in contrast to postsynaptic 5-HT_1A receptors, which mediate antidepressant effects. By blocking 5-HT_1A autoreceptors at doses that are selective for them over postsynaptic 5-HT_1A receptors, pindolol may be able to disinhibit serotonin release and thereby improve the antidepressant effects of SSRIs. The results of augmentation therapy with pindolol have been encouraging in early studies of low quality. A 2015

systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...

and

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of five

randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...

s 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". On the other hand, a 2017 systematic review indicated that pindolol's efficacy has been demonstrated in high evidence studies. Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact. Pindolol's antidepressive efficacy may predominently result from its ability to desensitize 5-HT_1A autoreceptors.

Others

* Pindolol is a potent scavenger of

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

. This effect is potentiated by

sodium bicarbonate Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3−) ...

. Inhibition of nitric oxide synthesis has an anxiolytic effect in animals. * Augmentation therapy of

premature ejaculation Premature ejaculation (PE) occurs when a man expels semen (and most likely experiences orgasm) soon after beginning sexual activity, and with minimal penile stimulation. It has also been called ''early ejaculation'', ''rapid ejaculation'', ''ra ...

: 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.

References

{{Serotonin receptor modulators Indoles 5-HT1A antagonists Antidepressants Antihypertensive agents Beta blockers Indole ethers at the benzene ring N-isopropyl-phenoxypropanolamines