Lisuride dopamine receptors

Bromocriptine (11), pergolide (12), cabergoline (13) and lisuride (14) are examples of compounds which have been developed in this way and are now used clinically. The pharmacological differences between the compounds is not very great. All are D2-dopamine receptor agonists, although... 

Figure 13.7. Chemical structure of some ergolines that have been or are currently used in the treatment of Parkinsonism. The outline structure of dopamine is also given to show why these drugs act as dopamine receptor agonists. The extended side chains in lisuride may also account for the action of the drug on 5-HT (particularly 5-HT2) receptors. The hallucinogenic effects of lisuride may be attributed to its action on central 5-HT2 receptors.

Dopamine receptor agonists. Striatal dopamine deficiency can be compensated by lysergic acid derivatives such as bromocriptine (p.116), lisuride, cabergoline, and pergolide and by the non-ergot compounds ropinirole and pramipexole. 

Dopamine receptor agonists include apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole and rotigotine. 

Lisuride is a dopamine receptor agonist that is used as an alternative drug in the treatment of Parkinson s disease. The pattern of adverse effects is similar to that seen with most of the ergot alkaloids (SEDA-10,118). The adverse effects that occurred after subcutaneous administration were so troublesome that the subcutaneous formulation was eventually unmarketable. 

Dopamine agonists. Recent studies point to the possibility of neuroprotection from aging and parkinsonism by the administration of dopamine receptor agonists. Agents showing some promise include bromocriptine, a-dihydroergocryptine, lisuride and pergolide. 

An alternative approach to the treatment with L-DOPA is the use of drugs that mimic the action of dopamine. Treatment with dopamine-agonists, such as bromocriptine (15),137 pergolide, and lisuride, has some advantages over treatment with L-DOPA. Dopamine agonists are effective in patients in the advanced stages of Parkinson s disease, unlike L-DOPA, because their action at postsynaptic dopamine receptors is unaffected by the lack of dopamine producing nerve cells. 

FIGURE 11.8. Structures selected dopamine receptor agonists (a) Bromocriptine, (b) Lisuride, (c) Piribedil, and (d) Ropinirole [52-55]. 

Another elegant example is the frans-selective reduction of lisuride (88) [67], reported by researchers at Sobering in the context of a synthesis of the partial dopamine receptor antagonist 89 (Equation 23) [68]. In this transformation, in situ deprotonation of the allylic urea side chain prevents its excision, which had been obsen/ed under catalytic hydrogenation conditions. 

Structurally closely related to LSD, Lisuride (226) is a compound having a 3,3-dimethylureido substituent, at die 9-position of the ergoline skeleton, and was first prepared in 1960 as a dopamine Dj-receptor agonist (98). Lisuride, as its acid maleate, is commercially available under Ae names of Cuvalit, Dopergin, Eunal, or Lysenyl, and is used clinically as an antimigraine and also as a prolactin inhibitor. The pharmacological activi and toxicity of lisuride were... 

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