Penbutolol

Medical uses

Penbutolol is used to treat mild to moderate high blood pressure.

It should not be used or only used with caution in people with heart failure and people with asthma. It may mask signs of low blood sugar in people with diabetes and it may mask signs of hyperthyroidism.

Animal studies showed some signs of potential trouble for women who are pregnant, and it has not been tested in women who are pregnant. It is not known if penbutolol is secreted in breast milk.

Side effects

Penbutolol has a low frequency of side effects. These side effects include dizziness, light headedness, and nausea.

Pharmacology

Pharmacodynamics

Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors (the two subtypes), thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.

Blocking β adrenergic receptors decreases the heart rate and cardiac output to lower arterial blood pressure. β blockers also decrease renin levels, which ultimately results in less water being reabsorbed by the kidneys and therefore a lower blood volume and blood pressure.

Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by a catecholamine, they stimulate a coupled G protein which activates adenylyl to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP ultimately alters the movement of calcium ions in heart muscle and increases heart rate.

The ability of penbutolol to act as a partial agonist proves useful in the prevention of bradycardia as a result of decreasing the heart rate excessively.

Like propranolol and pindolol, it is a serotonin 5-HT1A and 5-HT1B receptor antagonist; this discovery by several groups in the 1980s generated excitement among those doing research on the serotonin system as such antagonists were rare at that time.

Pharmacokinetics

Penbutolol is rapidly absorbed from the gastrointestinal tract, has a bioavailability over 90%, and has a rapid onset of effect. Penbutolol has a half life of five hours.

Chemistry

The experimental log P of penbutolol is 4.15. Penbutolol showed the second highest predicted lipophilicity of 30clinically relevant beta blockers, with the most lipophilic beta blocker predicted to be the lesser-known bopindolol.

Society and culture

Availability

Penbutolol was approved by the FDA in 1987. In January 2015 the FDA acknowledged that the penbutolol was no longer marketed in the US, and determined that the drug was not withdrawn for safety reasons.

References

References

1. FDA [https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf Penbutolol label] Last updated Dec 2010
2. Katzung, Bertram G. Basic and Clinical Pharmacology (13th ed.) McGraw-Hill Education, 2015. {{ISBN. 9780071826419
3. (1990). "Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism". Journal of Clinical Pharmacology.
4. (May 2025)
5. FDA notice in the Federal Register. Jan 9, 2015 [https://www.federalregister.gov/articles/2015/01/09/2015-00116/determination-that-tagamet-cimetidine-tablets-and-other-drug-products-were-not-withdrawn-from-sale Determination That TAGAMET (Cimetidine) Tablets and Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness]
6. Like other [[beta blockers]] it is not a first line treatment for this indication.NICE [https://www.nice.org.uk/guidance/cg127/chapter/1-guidance Hypertension guidance] Last updated 2013
7. (1982). "Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol". The Journal of Pharmacology and Experimental Therapeutics.
8. {{rp. 213–214 Penbutolol blocks this and decreases heart rate, which lowers blood pressure.Dent, M. R., Singal, T., Tappia, P. S., Sethi, R., Dhall, N. S. (2008). β-Adrenoceptor-Linked Signal Transduction Mechanisms in Congestive Heart Failure. Chapter 2, pp 27-49 in Signal transduction in the cardiovascular system in health and disease, Eds Srivastava, Ashok K., Anand-Srivastava, Madhu B. Springer Science & Business Media, 2008 {{ISBN. 9780387095523
9. 9780781771559
10. (1993). "Structural analysis by the comparative molecular field analysis method of the affinity of beta-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors". Eur. J. Pharmacol..
11. Glennon RA. Strategies for the Development of Selective Serotonergic Agents. Chapter 4 in The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics. Ed. Bryan L. Roth. Springer Science & Business Media, 2008 {{ISBN. 9781597450805
12. (1977). "Plasma level studies of penbutolol after oral dose in man". Journal of Clinical Pharmacology.
13. "Penbutolol".
14. (25 January 2012). "Penbutolol: Uses, Interactions, Mechanism of Action".
15. (February 2005). "The impact of lipophilicity in drug research: a case report on beta-blockers". Mini Rev Med Chem.