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 compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

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, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

and to treat heart failure following

cardiac surgery Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to corr ...

. 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 and ...

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 chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

, and

levosimendan Levosimendan (International Nonproprietary Name, 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 fol ...

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 do ...

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, in ...

. 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 pharmaceutical, scientific instruments and horticultural chemicals company headquartered in Ipswich, United Kingdom. It was listed on the London Stock Exchange and was once a constituent of the FTSE 100 Ind ...

, which licensed it to

Ipsen Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on transformative medicines in three therapeutic areas: oncology, rare disease and neuroscience. Ipsen is one of the world’s top 15 biopharmaceutical com ...

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

. 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, espec ...

, 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 is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

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 ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...

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 (HTN or HT), also known as high blood pressure (HBP), 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. Long-term high bl ...

, hemorrhage, respiratory failure, acute respiratory distress syndrome, pulmonary edema, pulmonary hypertension, and kidney failure. Like other ß2-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 abnor ...

hyperglycaemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

. 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 both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

. Effects of depexamine may be suppressed by concomitant use with ß2-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 The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

, does not cause vasoconstriction, and is not a

pressor agent Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...

. 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) 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. Catechol can be either a free molecule or a subst ...

. Its formula may be stated 4- -[46-[(2-phenylethy)aminohexyl.html" ;"title="6-[(2-phenylethy)amino.html" ;"title="-[46-[(2-phenylethy)amino">-[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, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

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