Penbutolol (Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin) is a medication in the class of beta blockers, used in the treatment of high blood pressure. 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 [1]. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors [2]. Penbutolol has also been found to be one of very few compounds that are 5-HT1A antagonists. 5-HT1A receptors are activated by serotonin, which have many different actions in different species. This makes it difficult to create generalizations about serotonin and its effects [1].
Hypertension
Hypertension can result from a multitude of alterations to blood volume, heart or kidney function. Hypertension involving a high heart rate can lead to myocardial ischemia [3]. Penbutolol acts by blocking β adrenergic receptors and blocking the sympathetic nervous system to decrease 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 [3].
β1 Blockade
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) [1]. The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases heart rate [4]. Penbutolol blocks this and decreases heart rate, which lowers blood pressure. 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 [2]. Penbutolol binding β1 adrenergic receptors also alters kidney functions. Under normal physiological conditions, the enzyme renin converts angiotensinogen to angiotensin I, which will then be converted to angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal gland, causing a decrease in electrolyte and water retention, ultimately increasing water excretion and decreasing blood volume and pressure [5].
Characteristics
Penbutolol is typically administered orally in doses of 20 mg per day [7]. It is rapidly absorbed from the gastrointestinal tract, has a bioavailability over 90% [6], and has a rapid onset of effect. Penbutolol has a half life of five hours [1], and a low frequency of side effects [7]. These side effects include dizziness, light headedness, and nausea [6]. When penbutolol is being metabolized, it undergoes a series of biotransformations, the main one being hydroxylation. One potential drawback of penbutolol is the inactivation of β2 adrenergic receptor, which makes this a less than ideal hypertensive treatment for people suffering from asthma or insulin dependent diabetes mellitus.
References
- Katzung, Bertram G. (1998). Basic and Clinical Pharmacology (7th ed.). London: Appleton & Lange. ISBN 0838505651
- Frishman, W. H., Covey, S. (1990). Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism. Journal of Clinical Pharmacology, 30(5):412-21
- Berdeaux, A., Duhaze, P., Giudicelli, J. F. (1982). Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol. The Journal of Pharmacology and Experimental Therapeutics, 221(3):740-747
- Dent, M. R., Singal, T., Tappia, P. S., Sethi, R., Dhall, N. S. (2008). Signal transduction in the cardiovascular system in health and disease. Advances in Biochemistry in Health and Disease, 3:27-49
- Howland, Richard D., Mycek, Mary J. (2006). Lippincott’s Illustrated Reviews: Pharmacology (3rd ed.). New York: Lippincott Williams & Wilkins. ISBN 0781741181
- Vallner, J. J., Jun H. W., Needham, T. E., Stewart, J. T., Brown, W., Frazer, H., Honigberg, I. L. (1977). Plasma level studies of penbutolol after oral dose in man. Journal of Clinical pharmacology, 17(4):231-23
- Schoenberger, J. A. (1989). Usefulness of penbutolol for systemic hypertension: Penbutolol