Dopa decarboxylase inhibitors are routinely used to potentiate the effects of
L-DOPA in the treatment of
Parkinson's disease. However, neither in clinical use nor in experimental models of
Parkinson's disease have the timing and dose of
dopa decarboxylase inhibitors been thoroughly explored. We now report on the choice of
dopa decarboxylase inhibitors, dose and the time of dosing relationships of
carbidopa,
benserazide and L-alpha-methyl
dopa (L-AMD) in potentiating the effects of
L-DOPA in the 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (
MPTP)-treated common marmoset. Pre-treatment with
benserazide for up to 3h did not alter the motor response to
L-DOPA compared to simultaneous administration with
L-DOPA. There was some evidence of a relationship between
carbidopa and
benserazide dose and increased locomotor activity and the reversal of motor disability. But in general, commonly used dose levels of
dopa decarboxylase inhibitors appeared to produce a maximal motor response to
L-DOPA. In contrast,
dyskinesia intensity and duration continued to increase with both
carbidopa and
benserazide dose. The novel
dopa decarboxylase inhibitor, L-AMD, increased locomotor activity and improved motor disability to the same extent as
carbidopa or
benserazide but importantly this was accompanied by significantly less
dyskinesia. This study shows that currently,
dopa decarboxylase inhibitors may be routinely employed in the
MPTP-treated primate at doses which are higher than those necessary to produce a maximal potentiation of the anti-parkinsonian effect of
L-DOPA. This may lead to excessive expression of
dyskinesia in this model of
Parkinson's disease and attention should be given to the dose regimens currently employed.