Theoretical Implications of the Use of L-Dopa in Parkinsonism.

The production of all the major symptoms of parkinsonism is attributed chiefly to the loss of the normal dopaminergic input into the striatum. This loss of dopaminergic input is due to degeneration of the cell bodies of the substantia nigra. An analogous loss of serotonin (5-hydroxytryptamine) may be of significance in the production of parkinsonian tremor. L-dopa ameliorates the symptoms of parkiusonism as a result of reinstitution of dopamine inhibition of the striatal neurons. L-dopa induced dyskinesias are felt to be related to denervation hypersensitivity of striatal neurons to dopamine produced by dopaminergic denervation. Failure to respond to L-dopa is related to degeneration of striatal dopaminergic receptors. The efficacy of amantadine hydrochloride is felt to be related to a block of the presynaptic reuptake of dopamine and thereby a prolongation of dopamine's effect at the receptor site.