Dopexamine is a synthetic analogue of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

that is administered intravenously in hospitals to reduce exacerbations of

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 to treat heart failure following cardiac surgery. It is not used often, as more established drugs like

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 ...

dobutamine Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection ...

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 ...

, and

levosimendan Levosimendan ( INN) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It is marketed under the trade name Simdax ( Orion Corporation). Overall the drug has a two fold mechanism of action. It leads ...

work as well. It works by stimulating beta-2 adrenergic receptors and peripheral

dopamine receptor D1 Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene. Tissue distribution D1 receptors are the most abundant kind of d ...

and

dopamine receptor D2 Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, ...

. It also inhibits the neuronal re-uptake of

. The most common adverse effects include fast heart beats and nausea. It was discovered by scientists at

Fisons Fisons plc was a British Multinational corporation, multinational pharmaceutical, scientific instruments and horticultural chemicals company headquartered in Ipswich, United Kingdom. It was listed on the London Stock Exchange and was once a cons ...

, which licensed it to

Ipsen Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on drug development and commercialization in three therapeutic areas: oncology, rare diseases and neuroscience. Ipsen is one of the world's top 15 biopha ...

in 1993, and Ipsen in turn licensed it to

Élan Elan Corporation plc was a major drugs firm based in Dublin, Ireland, which had major interests in the United States. It was listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN ...

in 1999. Ipsen licensed rights in North America and Japan to Circassia in 2008; the drug had never been approved in those countries. Dopexamine went off-patent in 2010.

Medical use

Dopexamine is used in hospitals as an inotropic agent to reduce exacerbations of

and to treat heart failure following cardiac surgery. It is administered intravenuously. As of 2010 dopexamine was not often administered in cardiac care because other, more well established drugs can accomplish the same effect, other such drugs include

, and

. It should not be used in people taking

monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

, nor in people who have certain adrenal cancers, low platelet counts, or people with left ventricular outlet obstruction. It also should not be used in people with severe

low blood pressure 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 ...

or reduced systemic vascular resistance. It should be used in caution in people with ischemic heart disease especially following heart attack or a recent episode of

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 ...

due to the risk of tachycardia. It should not be used in people with reduced blood volume. Safety in pregnant women has not been established.

Adverse effects

Very common (greater than 10%) adverse effects include fast heart beats and nausea. Common (between 1% and 10%) adverse effects include tremor, headache, transient

, vomiting, increased sweating, sepsis, sinus and nodal slow heart beat, cardiac arrest, myocardial infarction, cardiac enzyme changes, non-specific ECG changes,

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 ...

, hemorrhage, respiratory failure, acute respiratory distress syndrome, pulmonary edema, pulmonary hypertension, and kidney failure. Like other β2-agonists, dopexamine lowers potassium levels and raises glucose levels, so there is a risk of exacerbating

hypokalaemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an ...

hyperglycaemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluco ...

. People can develop

drug tolerance Drug tolerance or drug insensitivity is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further ...

to dopexamine if it is administered over a long period of time, as with other catecholamines. Dopexamine may potentiate the effects of other catecholamines like

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

. Effects of depexamine may be suppressed by concomitant use with β2-adrenergic and dopamine receptor antagonists requires caution.

Pharmacology

The half-life of IV dopexamine is 6–7 minutes in healthy adults and 11 minutes in patients with heart failure.

Mechanism of action

Dopexamine stimulates beta-2 adrenergic receptors and peripheral

and

. It also inhibits of neuronal re-uptake of

(Uptake-1). These activities increase cardiac output and increase blood flow to peripheral vascular beds. It is not an α-adrenergic agonist, does not cause vasoconstriction, and is not a pressor agent. As of 2004 there was some controversy surrounding the mechanism of dopexamine. Some held that its local effects of increased tissue perfusion were due only to increased output from the heart, while others held that were direct peripheral effects.

Chemistry

Dopexamine is a synthetic analogue of

, 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 ...

. Its formula may be stated 4- -[46-[(2-phenylethy)aminohexyl">6-[(2-phenylethy)amino.html" ;"title="-[46-[(2-phenylethy)amino">-[46-[(2-phenylethy)aminohexylmino]ethyl]-1,2-benzenediol or 4-[2-[46-(phenethylamino)hexyl]-amino]ethyl]pyrocatechol. Chinese manufacturers dominated the market for the active pharmaceutical ingredient as of 2015.

History

Dopexamine was discovered by scientists at

and Fisons received the USAN name dopexamine in 1985 for its compound, then called FPL 60278. The drug was marketed by 1992 and by 1996 had been approved in several countries. Fisons licensed the rights to

in 1993, and Ipsen in turn licensed the rights to Elan in 1999. The patent on dopexamine was controlled by Elan when it expired in 2003. Dopexamine was approved for use in the European Union for treatment of symptoms related to heart failure in 2010. In 2008 the UK company Circassia acquired the US, Canadian, and Japanese marketing rights to dopexamine from Ipsen; at the time, the company said it was planning to develop a new formulation of dopexamine in combination with fluids delivered via IV fluids, looking to improve outcomes following surgery. As of 2008 dopexamine had not been approved for any use in the US, Canada, or Japan. A Teva recalled batches of dopexamine in the UK in 2014 due to quality control issues by the manufacturer, Cephalon.

Research

Use in

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

has been explored in clinical trials, but use of an inotropic agent like

or dopexamine did not reduce mortality compared with

. Use of dopexamine may be harmful in sepsis

References

{{Monoamine reuptake inhibitors Beta-adrenergic agonists Cardiac stimulants Catecholamines D1 receptor agonists D2 receptor agonists Norepinephrine reuptake inhibitors