|Systematic (IUPAC) name|
|Routes||Oral, subcutaneous, transdermal|
|Bioavailability||10-20% for lisuride hydrogen maleate|
|Protein binding||about 15%|
|Excretion||renal and biliary in equal amounts|
|ATC code||G02 N02|
|Mol. mass||338.447 g/mol|
|(what is this?)|
Lisuride (Dopergin, Proclacam, Revanil) is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogen maleate salt.
Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the parkinsonian disability. Preliminary trials suggest the dermal application of lisuride may be useful in the treatment of Parkinson's disease. As lisuride is very poorly absorbed when take orally and has a short half-life, continuous transdermal administration offers significant advantages and could make the compound a far more consistent therapeutic. Lisuride is not currently available in the US, as the drug was not a commercial success in comparison with other dopamine receptor agonist antiparkinsonian compounds. It is still used clinically in a number of countries in the EU and is still commercially available in the UK and China.
Mode of action
Lisuride is a dopamine and a partial agonist for several serotonin receptors. It is an antagonist at the serotonin 5-HT2B receptor. It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A and 5-HT2A/C receptors. While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD, it lacks the psychedelic effects of its sister compound. Newer findings suggest the lack of psychedelic action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G-proteins are involved. Lisurid behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer. GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors.
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