✍ Scribed by Gilles Klopman; Aleksandr Sedykh
No coin nor oath required. For personal study only.
Background: Parkinson's disease is caused by a dopamine deficiency state in the fore brain area. Dopamine receptor agonists, MAO-B inhibitors, and N-Methyl-D-Aspartate (NMDA) receptor antagonists are known to have antiparkinson effect. Levodopa, a dopamine structural analog, is the best currently available medication for the treatment of Parkinsons disease. Unfortunately, it also induces side effects upon long administration time. Thus, multidrug therapy is often used, in which various adjuvants alleviate side effects of levodopa and enhance its antiparkinsonian action.
Results: Computer models have been created for three known antiparkinson mechanisms using the MCASE methodology. New drugs for Parkinsons disease can be designed on the basis of these models. We also speculate that the presence of biophores belonging to different groups can be beneficial and designed some potential drugs along this line. The proposed compounds bear pharmacophores of MAO-B inhibitors, dopamine agonists and NMDA antagonists, which could synergistically enhance their antiparkinson effect.
The methodology could readily be expanded to other endpoints where drugs with multiple activity mechanisms would be desirable.
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## Abstract Dyskinesias following long‐term dopamine replacement therapy are a major limitation of current treatments for Parkinson's disease. Recently, attention has been focused on the concept of using non‐dopaminergic adjuncts to currently available therapies in an attempt to reduce the problem