Penbutolol (brand names Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin) is a
medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
in the class of
beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...
s, used in the treatment of
high blood pressure
Hypertension, also known as high blood pressure, 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 itself. It is, however, a major ri ...
.FD Penbutolol label Last updated Dec 2010 Penbutolol is able to bind to both
beta-1 adrenergic receptor
The beta-1 adrenergic receptor (β1 adrenoceptor), also known as ADRB1, can refer to either the protein-encoding gene (gene ADRB1) or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric ...
s and
beta-2 adrenergic receptors
The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation ...
high blood pressure
Hypertension, also known as high blood pressure, 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 itself. It is, however, a major ri ...
. Like other
beta blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention). ...
it is not a first line treatment for this indication.
It should not be used or only used with caution in people with
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
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 beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation ...
(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
In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...
to lower
arterial 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 ...
. β blockers also decrease
renin
Renin ( etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin-angiotensin-aldosterone system (RAAS)—also known as the reni ...
levels, which ultimately results in less water being reabsorbed by the kidneys and therefore a lower
blood volume
Blood volume (volemia) is the volume of blood ( blood cells and plasma) in the circulatory system of any individual.
Humans
A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood p ...
and
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, 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 ...
.
Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by a
catecholamine
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Cate ...
, they stimulate a coupled
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...
which activates adenylyl to convert
adenosine triphosphate
Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...
(ATP) to
cyclic adenosine monophosphate
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine tri ...
(cAMP). The increase in cAMP ultimately alters the movement of calcium ions in heart muscle and increases heart rate. Penbutolol blocks this and decreases heart rate, which lowers blood pressure.
The ability of penbutolol to act as a
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
proves useful in the prevention of
bradycardia
Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...
as a result of decreasing the heart rate excessively. Penbutolol binding β1 adrenergic receptors also alters kidney functions. Under normal physiological conditions, the enzyme renin converts
angiotensinogen
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
to
angiotensin I
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...
, which will then be converted to
angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...
. Angiotensin II stimulates the release of
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...
from the
adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...
, causing a decrease in
electrolyte
An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...
and water retention, ultimately increasing water excretion and decreasing blood volume and pressure.Finkel, Richard; Clark, Michelle A.; Cubeddu, Luigi X. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition Lippincott Williams & Wilkins, 2009.
Like
propranolol
Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...
and
pindolol
Pindolol, sold under the brand name Visken among others, is a non-selective beta blocker which is used in the treatment of hypertension.Drugs.coInternational brand names for pindolol Page accessed Sept 4, 2015 It is also an antagonist of the se ...
, it is a
serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. 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.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
Pharmacokinetics
Penbutolol is rapidly absorbed from the gastrointestinal tract, has a
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
over 90%, and has a rapid onset of effect. Penbutolol has a
half life Half-life is a mathematical and scientific description of exponential or gradual decay.
Half-life, half life or halflife may also refer to:
Film
* ''Half-Life'' (film), a 2008 independent film by Jennifer Phang
* '' Half Life: A Parable for t ...
of five hours.
Chemistry
The experimental
log P
Log most often refers to:
* Trunk (botany), the stem and main wooden axis of a tree, called logs when cut
** Logging, cutting down trees for logs
** Firewood, logs used for fuel
** Lumber or timber, converted from wood logs
* Logarithm, in mathem ...
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.