Non-dopaminergic drug treatment of Parkinson's disease

Several lines of evidence suggest that substitution of the dopaminergic striatal deficit only represents one important aspect of the treatment of Parkinson's disease (PD) because neurotransmitter systems other than the dopaminergic one also degenerate and aggravate parkinsonian motor, vegetative and cognitive symptoms. Thus, regulation and balance of altered non-dopaminergic neurotransmission could provide an additional benefit for parkinsonian patients (PP). Moreover, onset of motor complications, psychosis and loss of drug efficacy increasingly reduce parkinsonian quality of life in the course of long-term dopamine substitution. Indirect stimulation of the dopaminergic neurotransmission via non-dopaminergic systems is an upcoming interesting strategy to solve these problems. Treatment of L-dopa-associated dyskinesias represents a further important future task of non-dopaminergic drug therapy. NMDA antagonists are a promising therapeutic option but further trials are necessary to elucidate their efficacy. A further peripheral effect of L-dopa/dopa decarboxylase inhibitor (DDI) application is increased homocysteine synthesis with its putative hypothetical additional central impact on neurodegeneration and progression of PD. Long-term monitoring with subsequent therapeutic decrease of homocysteine levels with folic acid could result in substantial clinical benefits at reasonable costs for PP. Also, it could hypothetically influence altered dopaminergic and non-dopaminergic neurotransmission beside its impact on occurrence of vascular disease and altered striatal microvascularisation in PD. The interesting field of non-dopaminergic drug therapy is emerging and will hopefully lead to a better understanding of PD and subsequently improve drug therapy of parkinsonian symptoms, which do not respond to dopaminergic substitution or are long-term complications of dopamine substitution.