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| Trade names | Visken, others[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a684032 |
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| Routes of administration | By mouth,intravenous |
| Drug class | Beta blocker;β-Adrenergic receptorantagonist;Non-selectiveβ1- andβ2-adrenergic receptorreceptor antagonist |
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| Pharmacokinetic data | |
| Bioavailability | 50% to 95% |
| Metabolism | Hepatic |
| Eliminationhalf-life | 3–4 hours |
| Excretion | Renal |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.033.501 |
| Chemical and physical data | |
| Formula | C14H20N2O2 |
| Molar mass | 248.326 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Pindolol, sold under the brand nameVisken among others, is anon-selectivebeta blocker which is used in the treatment ofhypertension.[1][2] It is also anantagonist of theserotonin5-HT1A receptor, preferentially blockinginhibitory 5-HT1Aautoreceptors, and has been researched as anadd-on therapy to various antidepressants, such asclomipramine and theselective serotonin reuptake inhibitors (SSRIs), in the treatment ofdepression[3][4][5] andobsessive–compulsive disorder (OCD).[6][7]
Pindolol is used forhypertension in theUnited States,Canada, andEurope, and also forangina pectoris outside the United States.[2] When used alone for hypertension, pindolol can significantly lowerblood pressure andheart 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 forarrhythmias andprophylaxis of acutestress reactions.[medical citation needed] It has been used to treatanxiety as well.[8][9]
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 hasintrinsic sympathomimetic activity and is therefore used with caution inangina pectoris.[10]
| 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-selectivebeta blocker in the class ofβ-adrenergic receptorantagonists. On the receptor level it is acompetitive partial agonist. It possessesintrinsic sympathomimetic activity, meaning it has some degree of agonist effects in the absence of competing ligands. Pindolol showsmembrane-stabilizing effects likequinidine, possibly accounting for its antiarrhythmic effects. It also acts as aserotonin5-HT1A receptorpartial agonist (intrinsic activity = 20–25%) or functionalantagonist.[32] The drug additionally showsaffinity for the serotonin5-HT1B receptor.[33]
Pindolol is rapidly and well-absorbed from thegastrointestinal tract. It undergoes somefirst-pass metabolism leading to anoralbioavailability of 50 to 95%. Patients withuremia may have a reduced bioavailability. Food does not alter the bioavailability, but may increase the resorption. Following an oral single dose of 20 mgpeak plasma concentrations are reached within 1 to 2 hours. The effect of pindolol on pulse rate (lowering) is evident after 3 hours.
The drug'svolume of distribution is 1.2 to 2 L/kg.[34] Theplasma protein binding is 40 to 60%.[34] It crosses theblood–brain barrier and can producecentrally mediatedside effects.[34] Despite being moderatelylipophilic, pindolol showed greaterelectroencephalogram (EEG) changes than the highly lipophilicpropranolol.[35] As a result, lipophilicity does not appear to be the sole determinant of blood–b rain barrierpermeability of beta blockers.[35]
Approximately two-thirds of pindolol is metabolized in the liver giving hydroxylates, which are found in the urine as gluconurides and ethereal sulfates. The remaining one-third of pindolol is excreted in urine in unchanged form.
Despite the rather shortelimination half-life of 3 to 4 hours,[34] hemodynamic effects persist for 24 hours after administration. The half-life is increased to 3 to 11.5 hours in patients withrenal impairment, to 7 to 15 hours in elderly patients, and from 2.5 to 30 hours in patients with liver cirrhosis.
The experimentallog P of pindolol is 1.75 to 1.9.[36][37] It is a moderatelylipophilic beta blocker.[34][38][35]
Pindolol was patented bySandoz in 1969 and was launched in the US in 1977.[39]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.
Pindolol has been investigated as anadd-on drug toantidepressant therapy with SSRIs likefluoxetine in the treatment ofdepression since 1994.[40][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 andsomatodendritic 5-HT1A receptors act asinhibitoryautoreceptors, inhibitserotoninrelease, 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 areselective 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 2015systematic review andmeta-analysis of fiverandomized 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.[41] Initiating pharmacotherapy with an SSRI plus pindolol might accelerate the SSRI's therapeutic impact.[4][41] Pindolol's antidepressive efficacy may predominantly result from its ability to desensitize 5-HT1A autoreceptors.[42]
Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
