Projects |
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Some general information on lisuride |
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| Lisuride, in contrast to all other marketed
ergot-derived drugs (such as pergolide, cabergoline, ergotamine etc.),
is an 8-α-ergoline (iso-ergoline),
a structure not found in natural ergot. It had been synthetized by M. Semonsky
(1) in former CSSR as a very potent peripheral serotonin (5-HT) antagonist
for migraine prophylaxis (Lysenyl®, Cuvalit® at a dose of 3 x 0.025 mg
p.o./day; in Germany marketing approval in 1977). Lisuride was discovered to be also a potent dopamine agonist (2) for
the treatment of hyperprolactinemia and pituitary tumours (marketed as
Dopergin® tablets (0.2 mg) since 1983) and Parkinson’s disease (Dopergin® 0.2
mg, 0.5 mg and 1.0 mg tablets since 1986 in various European and other
countries). For this reason there exists a large database for lisuride,
which also has become a standard (with more than 2000 publications) for
new research, due to its outstanding affinity (10-8 – 10-10 molar)
for some monoamine receptors (DA receptors as agonist or partial agonist,
5-HT1A receptors as agonist, 5-HT2A,
5-HT2B and 5-HT2C receptors
as antagonist (3)). The potent pure 5-HT2B antagonist action of lisuride explains why lisuride was shown to be effective in migraine prophylaxis, and why it is also devoid of any stimulatory action on trophic 5-HT2B receptors e.g. of the heart (in contrast to pergolide, cabergoline, nor-fenfluramine and 5-HT itself (as released from carcinoid tumours). In agreement with this, not a single case of cardiac valvulopathy has ever been reported (4) for lisuride (WHO and CSM database, Lisuride database covering at least 350 000 patients’ years of lisuride use). Whilst class label warnings had been issued by various European drug regulatory agencies (including the German BfArM) for all DA agonists regarding induction of hypersexuality and pathological gambling, no warning regarding cardiac valvulopathy has been given for lisuride (again in contrast to pergolide and cabergoline which had been found to carry an increased risk (5,6)). In his editorial in the same issue of the New Engl. J. Med., B.L. Roth states that “lisuride… which is not a 5-HT2B serotonin-receptor antagonist was not associated with valve disease. The findings concerning lisuride further implicate 5-HT2B serotonin-receptor activation as a key step in the progression of drug-induced valvulopathy…” (7). Thus it can be concluded that also in its new application forms (‘New Medical Entities’: lisuride patch and lisuride minipump), in addition to providing continuous dopaminergic stimulation (CDS) lisuride can also be considered as a drug with an excellent safety profile.
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