AMINOADAMANTANES AS NMDA RECEPTOR ANTAGONISTS AND ANTIPARKINSONIAN AGENTS - PRECLINICAL STUDIES

Aminoadamantanes such as 1-aminoadamantane (amantadine) and 1-amino-3, 5-dimethyladamantane (memantine) are N-methyl-D-aspartate (NMDA) recep tor antagonists which show antiparkinsonian-like activity in animal mo dels and in Parkinson's patients. The issue of whether NMDA antagonism plays a role in the symptomatological antiparkinsonian activity of am antadine and memantine is addressed by comparing: behaviourally effect ive doses, serum/brain levels, and their potency as NMDA receptor anta gonists. In the case of memantine, blockade of NMDA receptors is proba bly the only mechanism responsible for antiparkinsonian activity, wher eas for amantadine the situation is clearly far more complex. There ar e a number of differences between memantine and amantadine both in vit ro and in vivo, and although NMDA receptor antagonism certainly partic ipates in the antiparkinsonian activity of amantadine, other effects, some of which are elusive, also play a role. Moreover, it has been sug gested that the pathomechanism of Parkinson's disease involves excitot oxic processes and that treatment with NMDA receptor antagonists might also slow the progression of neurodegeneration. If this claim is true , such an effect could be achieved with amantadine and memantine which show neuroprotective activity in animals al therapeutically relevant doses. (C) 1997 Elsevier Science Ltd.