Felix-Martin Werner* and Rafael Coveñas Pages 124 - 134 ( 11 )
Background: Primary Parkinson syndrome is mostly treated by dopaminergic drugs, while the progression of the disease is not altered. Some non-dopaminergic are available, which are administered only after the Parkinsonian symptoms get worse.
Objective: The objective of this review is to give basic results in order to compare a dopaminergic and non-dopaminergic pharmacotherapy in Parkinson’s disease and to control whether the add-on pharmacotherapy with non-dopaminergic drugs can inhibit the progression of the disease.
Methods: In primary Parkinson syndrome, the altered activity of classical neurotransmitters and neuropeptides in the extrapyramidal system is summarized and up-dated. Anatomical studies on neural networks in the basal ganglia are mentioned. The direct, motor facilitatory pathway (D1 dopaminergic neurons) from the substantia nigra to the thalamus, via the internal globus pallidus, and the indirect, motor inhibitory pathway via D2 dopaminergic neurons have been considered. These established anatomical pathways have been brought in line with the neural interactions derived from neurotransmitter balances or imbalances. Besides, preclinical and clinical studies of effective non-dopaminergic anti-Parkinsonian drugs are reviewed.
Results: It can be hypothesized that glutamatergic neurons enhance dopamine deficiency in the substantia nigra and putamen through an increased presynaptic inhibition mediated by NMDA receptors. In the putamen, 5-HT2A serotonergic neurons counteract D2 dopaminergic neurons and A2A adenosine neurons antagonize D2 dopaminergic neurons by activating glutamatergic neurons, which presynaptically inhibit via subtype 5 of metabotropic glutamatergic receptors, D2 dopaminergic neurons. In the extrapyramidal system, an up-dated neural network, which harmonizes established anatomical pathways with derived neural interactions, is presented. In Parkinson’s disease, a question should be answered, whether a combination of dopaminergic and non-dopaminergic drugs can promote an increased motor and non-motor functioning.
Conclusion: A mono-target pharmacotherapy (using only dopaminergic drugs) and a multi-target pharmacotherapy (i.e. by combining dopaminergic and non-dopaminergic drugs) are compared. The alternate administration of dopaminergic and non-dopaminergic anti-Parkinsonian drugs, administered at different times during the day, must be tested in order to inhibit the progression of the disease. Assessment tools can be used to evaluate motor and cognitive functions. Moreover, imaging examination techniques can be also applied to control the course of the disease.
A2A adenosine antagonist, basal ganglia, dopamine, mono-dopaminergic pharmacotherapy, multi-target pharmacotherapy, neural network, NMDA receptor antagonist.
Institute of Neurosciences of Castilla y Leon (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), University of Salamanca, Salamanca, Institute of Neurosciences of Castilla y Leon (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), University of Salamanca, Salamanca