Dopamine Agonists

Dopamine Agonists Chemische Eigenschaften,Einsatz,Produktion Methoden

• Biologische Funktion

  Dopamine receptor agonists are considered by many clinicians as the first approach to therapy. They have a long duration of action and are less likely to cause dyskinesias than levodopa. The rationale for the use of dopamine agonists is that they provide a means of directly stimulating dopamine receptors and do not depend on the formation of dopamine from levodopa. As monotherapy, the dopamine agonists are less effective than levodopa but are often used early in the disease to delay initiation of levodopa therapy. When used as an adjunct to levodopa in advanced stages, the dopamine receptor agonists may contribute to clinical improvement and reduce levodopa dosage needs.
  The four dopamine agonists used in the United States are bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex), and ropinirole (Requip). Bromocriptine, an ergot derivative, is an agonist at the D₂-receptors and a partial D1-antagonist. Pergolide, also an ergot derivative, is an agonist at both D1- and D2- receptor subtypes. The more recently introduced nonergot drugs, ropinirole and pramipexole, are selective agonists at D₂-receptor sites.
  All four exert similar therapeutic effects and can produce the same adverse effects seen with levodopa. The differences between the ergot derivatives and the newer agents reside primarily in their adverse effects and tolerability. Postural hypotension, nausea, somnolence, and fatigue are common adverse effects of bromocriptine and pergolide therapy and can limit the use of these drugs.
  Because of these adverse effects, the drugs are generally first administered at low doses and then the dose is gradually increased over weeks or months as tolerance to the adverse effects develops. These symptoms are generally less frequent and less severe with pramipexole and ropinirole, which allows for a more rapid achievement of therapeutic response. Also, because pramipexole and ropinirole are better tolerated, they are increasingly used as monotherapy.

• Allgemeine Beschreibung

  The addition of DA agonists to levodopa therapy has gainedwidespread popularity in the treatment of PD.DA agonistsnot only produce less dyskinesia, but also have been hypothesizedto slow the progressive degeneration of DA neurons.36 DA agonists are classified into ergot derivatives(pergolide, cabergoline, and bromocriptine) and nonergotderivatives (apomorphine, pramipexole, ropinirole, androtigotine).