MEMANTINE, AMANTADINE, AND L-DEPRENYL POTENTIATE THE ACTION OF L-DOPAIN MONOAMINE-DEPLETED RATS

Some treatments used for Parkinson's disease attenuate locomotor depre ssion in rats treated with reserpine and cr-methyl-p-tyrosine. In the present study memantine (2.5, 5.0 mg/kg), amantadine (10, 20 mg/kg) (b oth uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; M AO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0 mg/kg) and L-DOPA (50, 100 mg/kg, + benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10 mg/kg) and L-DO PA (100, 200 mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pro nounced increase in locomotor activity when given alone. The combinati on of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was see n. On the other hand the combination of these agents with L-DOPA produ ced a pronounced synergistic effect. Hence, the clinical observation t hat coadministration of L-DOPA with either memantine or amantadine res ults in enhancement of their action is also reflected in an animal mod el of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of s ide effects and may also be predicted to have additional benefits rela ted to the neuroprotective properties of memantine, amantadine, and L- deprenyl.