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| Formula | C22H32N2O2 |
| Molar mass | 356.510 g·mol−1 |
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Dopexamine is a synthetic analogue ofdopamine that is administered intravenously in hospitals to reduce exacerbations ofheart failure and to treat heart failure followingcardiac surgery. It is not used often, as more established drugs likeepinephrine,dopamine,dobutamine,norepinephrine, andlevosimendan work as well. It works by stimulatingbeta-2 adrenergic receptors and peripheraldopamine receptor D1 anddopamine receptor D2. It also inhibits the neuronal re-uptake ofnorepinephrine.
The most common adverse effects includefast heart beats and nausea.
It was discovered by scientists atFisons, which licensed it toIpsen in 1993, and Ipsen in turn licensed it toÉlan 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.
Dopexamine is used in hospitals as aninotropic agent to reduce exacerbations ofheart failure and to treat heart failure followingcardiac surgery.[1][2][3] It is administered intravenuously.[2]
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 includeepinephrine,dopamine,dobutamine,norepinephrine, andlevosimendan.[4]
It should not be used in people takingmonoamine oxidase inhibitors, nor in people who have certainadrenal cancers,low platelet counts, or people with leftventricular outlet obstruction.[2]
It also should not be used in people with severelow blood pressure 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 ofangina due to the risk of tachycardia. It should not be used in people withreduced blood volume.[2]
Safety in pregnant women has not been established.[2]
Very common (greater than 10%) adverse effects includefast heart beats and nausea.[2]Common (between 1% and 10%) adverse effects include tremor, headache, transientlow blood pressure, vomiting, increased sweating, sepsis, sinus and nodalslow heart beat, cardiac arrest, myocardial infarction, cardiac enzyme changes, non-specific ECG changes,high blood pressure, hemorrhage, respiratory failure, acute respiratory distress syndrome, pulmonary edema, pulmonary hypertension, and kidney failure.[2]
Like other β2-agonists, dopexamine lowers potassium levels and raises glucose levels, so there is a risk of exacerbatinghypokalaemia orhyperglycaemia.[2]
People can developdrug tolerance to dopexamine if it is administered over a long period of time, as with other catecholamines.[2]
Dopexamine may potentiate the effects of other catecholamines likenoradrenaline. Effects of depexamine may be suppressed by concomitant use with β2-adrenergic and dopamine receptor antagonists requires caution.[2]
The half-life of IV dopexamine is 6–7 minutes in healthy adults and 11 minutes in patients with heart failure.[2]
Dopexamine stimulatesbeta-2 adrenergic receptors and peripheraldopamine receptor D1 anddopamine receptor D2. It also inhibits of neuronal re-uptake ofnorepinephrine (Uptake-1). These activities increase cardiac output and increase blood flow to peripheral vascular beds.[2][3] It is not anα-adrenergic agonist, does not cause vasoconstriction, and is not apressor agent.[2]
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.[5]
Dopexamine is a synthetic analogue ofdopamine, acatecholamine.[3] Its formula may be stated 4-[2-[4[[6-[(2-phenylethy)amino]-hexyl]amino]ethyl]-1,2-benzenediol or 4-[2-[4[[6-(phenethylamino)hexyl]-amino]ethyl]pyrocatechol.[6]
Chinese manufacturers dominated the market for theactive pharmaceutical ingredient as of 2015.[7]
Dopexamine was discovered by scientists atFisons[8][9] and Fisons received the USAN name dopexamine in 1985 for its compound, then called FPL 60278.[6]
The drug was marketed by 1992[10] and by 1996 had been approved in several countries.[11]
Fisons licensed the rights toIpsen in 1993, and Ipsen in turn licensed the rights to Elan in 1999.[8]
The patent on dopexamine was controlled by Elan when it expired in 2003.[12]
Dopexamine was approved for use in the European Union for treatment of symptoms related to heart failure in 2010.[2]
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.[13] As of 2008 dopexamine had not been approved for any use in the US, Canada, or Japan.[13] A
Teva recalled batches of dopexamine in the UK in 2014 due to quality control issues by the manufacturer, Cephalon.[14]
Use insepsis has been explored in clinical trials, but use of an inotropic agent likedobutamine or dopexamine did not reduce mortality compared withnorepinephrine orepinephrine.[15] Use of dopexamine may be harmful in sepsis[5]
