Lisuride

1,1- diethyl- 3-( 9,10- didehydro - 6-methyl- 8α - ergolinyl ) urea

• C20H26N4O
• C20H26N4O · C4H8O4 ( maleate )

N02CA07 G02CB02

Dopamine, serotonin agonist, 5 - HT2B antagonist

• 338.45 g · mol -1
• 454.52 g · mol -1 ( maleate )

Template: Infobox chemical / molecular formula search available

Lisuride is a drug which is used in the treatment of Parkinson's disease, in the prophylaxis of migraine and as a prolactin inhibitor weaning. Lisuride is sold in Germany under the brand name DOPERGIN ® and is subject to medical prescription.

Chemistry

Lisuride is a derivative of ergot alkaloids drug with a Ergo Ling round scaffolding. However, it differs from naturally occurring Ergolinen, such as ergotamine, by a ( 8S ) - configuration in the Ergo Ling round scaffolding.

With terguride and mesulergine two structurally related compounds of lisuride are known, which have been clinically tested.

The representation of lisuride is done by a Hofmann, Curtius or Lossen rearrangement of lysergic acid, followed by acylation of the racemate and ( 8S ) -amino group with diethylcarbamoyl.

Pharmacology

Areas of application

Lisuride was developed as Migräneprophylaktikum. For this indication is in Germany no more approval. Lisuride is now used primarily in combination with levodopa in patients with Parkinson's disease. Other applications include restless legs syndrome, neuroleptic malignant syndrome, primary and secondary weaning, galactorrhea, amenorrhea, and prolaktinbedingte acromegaly.

Mechanism of Action

Lisuride applies as many ergoline as a "dirty drug", as it interacts with many receptors, such as dopamine receptors, serotonin receptors, adrenergic receptors. In contrast to all other therapeutically used Mutterkornalkaloidderivaten lisuride also shows a high affinity for histamine receptors and beta adrenergic receptors.

For its clinical efficacy in the treatment of Parkinson 's disease interaction is blamed with dopamine receptors. It acts as a partial agonist lisuride (dopamine agonist ) to the dopamine receptors subtypes D2/3/4 and furthermore also the subtypes D1 / 5 and can thus eliminate the dopamine deficiency symptoms of Parkinson's disease. Moreover performs a lisuride -induced stimulation of dopamine receptors of the pituitary gland to inhibit the release of the hormone prolactin, and thus to an inhibition of milk production.

On serotonin receptors subtype 5 - HT2B lisuride acts as an antagonist. With inhibition of these receptors its efficacy in the prophylaxis of migraine is associated. At the serotonin receptors of the subtype 5 -HT1A and 5- HT2A / C it acts as a partial agonist. The serotonin receptors subtype 5 - HT1B / D lisuride is also affine, if it thereby acts as an agonist or antagonist is not released.

Side effects

Occur especially at the start of therapy, at too high a dose or dose increase, or when taking without concomitant meal may include nausea, fatigue, drowsiness, dizziness, headache, sweating, dry mouth and sudden drop in blood pressure and in rare cases, vomiting and also Retroperitonealfibrosen.

In animal studies, lisuride dissolves in male rats from premature ejaculation. In female as well as in early castrated male rats, administration of lisuride leads shortly after birth or during puberty for training male behavior patterns.

Interactions

The sedative effect of the preparation can be enhanced by other, on the central nervous system depressant effect drugs. With simultaneous use with neuroleptics and other dopamine antagonists a reciprocal effect slowdown is to be expected.

Trade names

Lisuride in Germany and Austria under the name DOPERGIN commercially available.