Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic

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 ...

which is used in the treatment of acute

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 ...

(slow heart rate),

heart block Heart block (HB) is a disorder in the heart's rhythm due to a fault in the natural pacemaker. This is caused by an obstruction – a block – in the electrical conduction system of the heart. Sometimes a disorder can be inherited. Despite the ...

, and rarely for

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

, among other indications. It is used by injection into a vein,

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

fat In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food. The term often refers specif ...

, or the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

, by

inhalation Inhalation (or inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

, and in the past under the tongue or into the rectum. Side effects of isoprenaline include rapid heart beat, heart palpitations, and

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

s, among others. Isoprenaline is a selective

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the β-adrenergic receptors, including both the β₁- and β₂-adrenergic receptors. By activating these

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s, it increases

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

and the force of heart contractions. Chemically, isoprenaline is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

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 ...

and is the ''N''-

isopropyl In organic chemistry, a propyl group is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent ...

analogue of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(noradrenaline) and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

(adrenaline). Isoprenaline was one of the first

sympathomimetic

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s and was the first selective β-adrenergic receptor agonist. The medication was discovered in 1940 and was introduced for medical use in 1947.

Medical uses

Isoprenaline is used to treat

and episodes of Adams–Stokes syndrome that are not caused by

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...

or fibrillation, in emergencies for

cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...

until

electric shock An electrical injury (electric injury) or electrical shock (electric shock) is damage sustained to the skin or internal organs on direct contact with an electric current. The injury depends on the Current density, density of the current, tissu ...

can be administered, for

bronchospasm Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylat ...

occurring during

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

, and as an adjunct in the treatment of

hypovolemic shock Hypovolemic shock is a form of Shock (circulatory), shock caused by severe hypovolemia (insufficient blood volume or extracellular fluid in the body). It can be caused by severe dehydration or blood loss. Hypovolemic shock is a medical emergency ...

septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...

, low

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 ...

(

hypoperfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion may also refer to fixation via perfusion, used in ...

) states,

congestive 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 fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

, and

cardiogenic shock Cardiogenic shock is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the heart. Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased ...

. It is also used to prevent

Torsades de Pointes ''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP; also called ''torsades'') (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorph ...

in patients with long QT refractory to

magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium. Isoprenaline is used in the acute management of bradycardia, though not in the chronic treatment of bradycardia. Historically, it was used to treat

via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations. The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction.

Available forms

Many formulations of isoprenaline appear to have been discontinued in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

and many other countries. In the United States, it remains available only as an injectable

solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Solu ...

. It was previously also available in the United States as a solution, metered

aerosol An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be generated from natural or Human impact on the environment, human causes. The term ''aerosol'' co ...

, powder, or disc for

and as a tablet for

sublingual Sublingual (List of abbreviations used in medical prescriptions, abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through Tissue (biology), t ...

and

rectal administration Rectal administration (colloquially known as boofing or plugging) uses the rectum as a route of administration for medication and other fluids, which are absorbed by the rectum's blood vessels,The rectum has numerous blood vessels available to a ...

, but these formulations were discontinued.

Contraindications

It should not be used in people with

tachyarrhythmia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the Heart rate#Resting heart rate, normal resting rate. In general, a resting heart rate over 100 pulse, beats per minute is accepted as tachycardia in adults. Heart rates a ...

s (except in special circumstances),

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

caused by

digitalis ''Digitalis'' ( or ) is a genus of about 20 species of herbaceous perennial plants, shrubs, and Biennial plant, biennials, commonly called foxgloves. ''Digitalis'' is native to Europe, Western Asia, and northwestern Africa. The flowers are ...

poisoning, ventricular arrhythmias which require

inotropic An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular co ...

therapy, or with

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

Side effects

Side effects of isoprenaline may include

nervousness Anxiety is an emotion characterised by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different from fear in that fear is defined as the emotional response to a present threat, where ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...

palpitations Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...

, Adams-Stokes attacks,

pulmonary edema Pulmonary edema (British English: oedema), also known as pulmonary congestion, is excessive fluid accumulation in the tissue or air spaces (usually alveoli) of the lungs. This leads to impaired gas exchange, most often leading to shortness ...

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

, ventricular arrhythmias,

s, difficulty breathing,

sweating Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distributed over much of the ...

, mild

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

, flushing, and

pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eye ...

. Isoprenaline has been reported to cause

insulin resistance Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia. Insulin is a horm ...

leading to

diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening acute complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally ...

Overdose

Overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

of isoprenaline may produce effects including

s, palpitations,

, and myocardial necrosis.

Pharmacology

Pharmacodynamics

Isoprenaline is a β₁- and β₂-adrenergic receptor

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...

and has almost no activity at the α-adrenergic receptors at lower concentrations. It has similar

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the β₁- and β₂-adrenergic receptors. At higher concentrations, isoprenaline can also evoke responses mediated by α-adrenergic receptors. Its agonist effects at the

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

(TAAR1) additionally provide it with

pharmacodynamic Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

effects that resemble those of the endogenous

trace amine Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...

s, like

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the bl ...

. Isoprenaline's effects on the

cardiovascular system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

(non-selective) relate to its actions on

cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...

β₁-adrenergic receptors and β₂-adrenergic receptors on

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

within the

tunica media The tunica media (Neo-Latin "middle coat"), or media for short, is the middle tunica (layer) of an artery or vein. It lies between the internal elastic lamina of the tunica intima on the inside and the tunica externa on the outside. Artery The ...

arteriole An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillary, capillaries. Arterioles have vascular smooth muscle, muscular walls (usually only one to two layers of smoo ...

s. Isoprenaline has positive inotropic and

chronotropic Chronotropic effects (from ''chrono-'', meaning time, and ''tropos'', "a turn") are those that change the heart rate. Chronotropic drugs may change the heart rate and cardiac cycle, rhythm by affecting the electrical conduction system of the hea ...

effects on the heart. β₂-Adrenergic receptor stimulation in arteriolar smooth muscle induces

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

. Its inotropic and chronotropic effects elevate systolic

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 ...

, while its vasodilatory effects tend to lower diastolic blood pressure. The overall effect is to decrease

mean arterial pressure In medicine, the mean arterial pressure (MAP) is an average calculated blood pressure in an individual during a single cardiac cycle. Although methods of estimating MAP vary, a common calculation is to take one-third of the pulse pressure (the d ...

due to the vasodilation caused by β₂-adrenergic receptor activation. The

isopropylamine Isopropylamine (also known as monoisopropyl amine, MIPA, or 2-propylamine) is an organic compound, an amine. It is a hygroscopic colorless liquid with ammonia-like odor. It is miscible with water and flammable. It is a valuable intermediate in c ...

group in isoprenaline makes it selective for β-adrenergic receptors. The adverse effects of isoprenaline are also related to the drug's

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

effects. Isoprenaline can produce

(an elevated

), which predisposes people who take it to

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beat ...

Pharmacokinetics

Absorption

Data on the absorption of isoprenaline are limited.

Oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

isoprenaline is well-absorbed but is subject to strong

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

and is approximately 1,000times less potent than

intravenous administration Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Hence, its oral

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 ...

is very low. Another study suggested that its oral bioavailability, based on

activity via different routes, was slightly less than 4%.

Distribution

Isoprenaline is minimally able to cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

and hence is a

peripherally selective drug Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest o ...

. This is attributed to its high hydrophilicity. Whereas the extraction of isoprenaline in a single passage of the brain circulation following

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

in humans was 3.8%, the extraction of propranolol, which is a more

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

compound and is readily able to cross into the brain, was 63.0%. The

plasma protein binding Plasma protein binding refers to the degree to which medications attach to blood proteins within the blood plasma. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse o ...

of isoprenaline is 68.8 ± 1.2%. It is bound mainly to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

Metabolism

Isoprenaline is

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

by catechol ''O''-methyltransferase (COMT) and

conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form *Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change o ...

sulfation Sulfation (sometimes spelled sulphation in British English) is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected ...

. It does not appear to be glucuronidated. There is very large interindividual variability in the sulfation of isoprenaline. The free

catechol Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amounts. It ...

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

groups keep it susceptible to enzymatic metabolism. The drug is a poor

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

for

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

(MAO) and is not metabolized by this enzyme. This is in contrast to

and

. Isoprenaline is much more strongly metabolized and conjugated with oral administration than with intravenous administration. Its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

3-''O''-methylisoprenaline, formed by COMT, is active as a weak β-adrenergic receptor antagonist.

Elimination

Isoprenaline is excreted primarily in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

, as

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

conjugates. It is excreted 59 to 107% in urine and 12 to 27% in

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

. A majority of isoprenaline is excreted in urine in conjugated form, whereas 6.5 to 16.2% is excreted as unchanged isoprenaline and 2.6 to 11.4% is excreted as 3-O-methylisoprenaline and conjugates. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of isoprenaline by

is approximately 2.5 to 5minutes. Its half-life with

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

is approximately 40minutes.

Chemistry

Isoprenaline, also known as ''N''-isopropyl-3,4,β-trihydroxyphenethylamine or as ''N''-isopropylnorepinephrine, is a

substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...

and

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is the ''N''-

analogue of

(3,4,β-trihydroxyphenethylamine) and

(3,4,β-trihydroxy-''N''-methylphenethylamine). Isoprenaline is a small-molecule compound with the

molecular formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as paren ...

C₁₁H₁₇NO₃ and a

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

of 211.26g/mol. It is a

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

compound with a predicted log P of -0.6 to 0.25. For comparison, the experimental log P values of epinephrine and norepinephrine are -1.37 and -1.24, respectively. Isoprenaline is used pharmaceutically as the hydrochloride and

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

s. It is also used to a much lesser extent as the free base. Isoprenaline is a

racemic mixture In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

levorotatory Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

and dextrorotatory

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

s. The levorotatory or (''R'')-enantiomer of isoprenaline is known as levisoprenaline () but was never marketed. Synthetic analogues closely related to isoprenaline include arbutamine, dichloroisoprenaline (dichloroisoproterenol), hexoprenaline, isoetharine (α-ethylisoprenaline), orciprenaline (metaproterenol; a positional isomer of isoprenaline), prenalterol, and soterenol (3-methanesulfonamidylisoprenaline), among others.

History

Isoprenaline was discovered in 1940 and was developed in the 1940s. It was first approved for medical use in 1947 in the United States. Isoprenaline was one of the first

sympathomimetic

s, was the first selective β-adrenergic receptor agonist, and was the first major sympathomimetic agent devoid of pressor effects. Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to unintentional

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

: the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the United States and Canada, where the deaths were not observed. The short

duration of action Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

and poor

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

activity of isoprenaline led to the development of the much longer-acting and orally active orciprenaline (metaproterenol).

Society and culture

Names

''Isoprenaline'' is the major generic name of the drug and its , , and . ''Isoprenalina'' is its

Italian Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, a Romance ethnic group related to or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance languag ...

generic name and its . ''Isoprenaline hydrochloride'' and ''isoprenaline sulfate'' are its in the case of the hydrochloride and

s, respectively. ''Isoproterenol'' is another important synonym of the drug. ''Isoproterenol hydrochloride'' is its and in the case of the hydrochloride salt and ''isoproterenol sulfate'' is its and in the case of the sulfate salt. Other synonyms of the drug include ''isopropylnorepinephrine'', ''isopropylnoradrenaline'', and ''isopropydine''. It is additionally known by the former developmental code name ''WIN-5162''. Isoprenaline has been marketed under many brand names worldwide. These include Aleudrina, Asthpul, Iludrin, Iprenol, Isomenyl, Isuprel, Isoprenaline, Isoprenalina, Isoproterenol, Neo-Epinine, Neodrenal, Proternol, and Saventrine, among others. It is also marketed as a

combination drug A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

with cromoglicic acid as Frenal Compositum, in combination with pronase as Isopal P, and in combination with

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

as Stmerin D.

References

{{Phenethylamines Antiasthmatic drugs Alpha-adrenergic agonists Beta1-adrenergic agonists Beta2-adrenergic agonists Bronchodilators Cardiac stimulants Catecholamines Chemical substances for emergency medicine Drugs acting on the cardiovascular system Inotropic agents Isopropylamino compounds Peripherally selective drugs Phenylethanolamines Sympathomimetic amines TAAR1 agonists Vasodilators