Dopaminergic agonists
Dopaminergic agonists stimulate dopaminergic receptors.Generally, agonists which do not cross the blood-brain barrier have peripheral effects and agonists which penetrate well into the brain have mainly central effects.
Dopaminergic agonists with peripheral effects
The principal dopaminergic agonist is dopamine. Dopamine, administered by intravenous route, has only peripheral effects because it does not penetrate into the brain. The vomiting effect of dopamine is explained by stimulation of Area postrema which is accessible to dopamine without crossing the blood-brain barrier.
Effects
The effects of dopamine depend on the administered dose:
- In low doses, it stimulates specific dopaminergic receptors and induces renal, mesenteric and coronary vasodilation and an increase in diuresis and natriuresis.
- In moderate doses, it stimulates beta receptors resulting in a positive inotropic effect and a vasodilation.
- In large doses, it can stimulate alpha- adrenergic receptors inducing a vasoconstriction and cause a release of norepinephrine.
Use
Dopamine is used in the treatment of hemodynamic disorders, acute heart failure, as occurs in cardiogenic shock and myocardial infarction and in treatment of low cardiac output syndrome. It is administered by intravenous perfusion under monitoring of various parameters: arterial pressure, heart rate…
Its adverse effects are observed especially in case of overdose: nausea, vomiting, rise in blood pressure, heart rate disorders, exhaustion of effect.
Dopexamine is an agonist of dopaminergic receptors and beta-2 adrenergic receptors, which is used in short term treatment of acute congestive heart failure.
Dopaminergic agonists with neurological and endocrine central effects
Dopaminergic agonists which cross the blood-brain barrier have central effects of neurological and endocrine types. They are used in the treatment of Parkinson's disease and hyperprolactinemia
These agonists are ergot derivatives such as bromocriptine, lisuride, pergolide and cabergoline or molecules non derived from ergot such as apomorphine, piribedil, quinagolide, ropinirole and pramipexole.
- Bromocriptine
Bromocriptine is an ergot derivative which stimulates D1 and particularly D2 dopaminergic receptors. It is used:
- in treatment of Parkinson's disease for replacing endogenous dopamine whose secretion is defective.
- in treatment of various hormonal disorders: it inhibits prolactin secretion by the pituitary gland and is used in the treatment of galactorrhea, sterility, amenorrhea and inhibition of lactation. Injectable depot formulations can be used in the treatment of non surgically curable pituitary microadenoma.
The responsibility of bromocriptine in the outbreak of cardiovascular or neurological adverse effects when it is used to inhibit lactation was suspected and its use in this therapeutic indication criticized.
- Lisuride and Pergolide
Lisuride and pergolide, like bromocriptine, are ergot derivatives and they have overall similar pharmacological properties. Lisuride and pergolide have, in experiments, antiinflammatory properties by incompletely elucidated mechanisms. Lisuride is used in the treatment of Parkinson's disease, lactation inhibition and hyperprolactinemia (galactorrhea, gynecomastia).
Pergolide |
PERMAX* Tablets |
- Cabergoline
Cabergoline is an ergot derivative, rather selective D2 receptor agonist. It is a powerful inhibitor of prolactin secretion . It reduces also the intensity of symptoms of Parkinson's disease. It is used in the treatment of hyperprolactinemia. It can be prescribed in the treatment of female sterility due to hyperprolactinemia. Cabergoline has a very long duration of action and can be given only once per week. Its possible teratogenicity (which seems low) must be considered and conception avoided for at least one month after ceasing treatment.
Cabergoline |
DOSTINEX* Tablets |
- Quinagolide
Quinagolide is obtained by chemical synthesis. Its chemical structure has similarities with that of ergot derivatives and that of apomorphine. It is a specific agonist of D2 dopaminergic receptors. Its principal effect is to reduce prolactin secretion and its principal therapeutic use the treatment of hyperprolactinemia and of its clinical consequences. It can be used for prevention of puerperal lactation. It is used in very low dose, 25 to 150 microgram per day, by oral route.
Its most frequent adverse effects are nausea, sometimes vomiting. Exceptionally and especially in case of overdose, it can induce a psychotic syndrome with hallucinations.
- Apomorphine
Apomorphine (thus called because it was obtained by action of concentrated hydrochloric acid on morphine) stimulates D1 and D2 dopaminergic receptors. It has an emetic effect and was used to elicit vomiting in subjects having absorbed toxic compounds by oral route but this use is not advised now.
It is used as antiparkinsonian, in particular to correct fluctuations of effects of L-dopa, called “one-off”. It has an immediate effect but of short duration, approximately an hour.
Apomorphine |
APOKYN Injection, subcutaneous |
Apomorphine, in the form of sublingual tablets, is used in the treatment of erectile dysfunction where it is generally less effective than 5-phosphodiesterases inhibitors such as sildenafil.
- Ropinirole
Ropinirole, not an ergot derivative, is a D3 and to a lesser degree D2 dopaminergic receptor agonist, used in the treatment of the Parkinson's disease. At the beginning of treatment, the dosage must be increased gradually until it appears optimal. The most frequent adverse effects are nausea and drowsiness. Ropinirole might give less dyskinesia than L-DOPA.. But, like other drugs of this group, it can cause sudden onset of sleep which is rare but can have serious consequences.
Ropinirole |
REQUIP* tablets |
- Pramipexole is a D3 and to a lesser degree D2 dopaminergic receptor agonist. Pramipexole could have, according to experimental studies, a neuroprotector effect.. It can induce various adverse effects among which hallucinations and sudden onset of sleep.
Pramipexole |
MIRAPEX* Tablets |
- Piribedil
Piribedil is a dopaminomimetic drug proposed for peripheral (arteriopathies) and central disorders (Parkinson's disease, strokes)
Dopaminergic agonists with central effects have common adverse effects but whose frequency and importance differ according the product, its dosage and duration of treatment. There are digestive disorders: nausea, vomiting; cardiovascular disorders: hypertension, hypotension, palpitations and with ergot derivatives cardiac valvulopathies; neuropsychiatric disorders: drowsiness, dyskinesia, confusional state, hallucinations, sudden onset of sleep.
In the event of severe adverse effects, transitory or permanent discontinuation of the responsible drug is necessary. It is possible to use an antagonist of dopaminergic receptors, either with peripheral effects like domperidone, or with central effects like a neuroleptic agent.
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