Abstract
In this review, the altered functions of neurotransmitters and neuropeptides in the extrapyramidal system in primary Parkinson syndrome are pointed out. In this syndrome, an altered neurotransmitter balance in the nuclei of the extrapyramidal system with hypoactivity of the dopaminergic and GABAergic neurotransmitter systems and hypoactivity of the muscarinic cholinergic and glutamatergic neurotransmitter systems occurs. Serotonin counteracts dopamine deficiency in the putamen via 5-HT2A receptors. Neuropeptides have a modulating function and influence the mentioned neurotransmitter systems. Neurotensin antagonists, at NTS1 receptors, and antagonists, at the mu opioid receptor, could have a therapeutic function in the anti-Parkinsonian pharmacotherapy. A scheme including the possible neural combinations in the neuronal system and considering the mentioned alterations of the neuroactive substances is described. A scientific problem to be investigated is, whether a multi-target pharmacological treatment, i.e. add-on drugs such as agonists of the s2 nicotinic cholinergic receptor, A2A adenosine antagonists, 5 metabotropic glutamatergic receptor antagonists and/or NTS1 receptor antagonists could exert a neuroprotective effect on dopaminergic neurons and may be slow down the progression of the disease. In clinical studies with Parkinsonian patients, a main goal must be to compare a cohort of Parkinsonian patients receiving a mono-dopaminergic pharmacotherapy with patients receiving multi-target anti-Parkinsonian pharmacotherapy. The motor and cognitive functions could be assessed by assessment tools, and imaging examination techniques should be applied in order to assess the generally progressive course of the illness.
Highlights
Primary Parkinson syndrome is a progressive neurologial disease
According to the literature on Parkinson’s disease and on the interactions of the involved neuroactive substances in the extrapyramidal system, the possible neural pathways are shown in Figure 1: dopaminergic neurons originating in the substantia nigra pars compacta, showing a low activity, transmit a weak activating potential, via D1 and D2 receptors, to other dopaminergic neurons placed in the nucleus caudatus
Enzyme, whereas the second group should obtain a combination of different anti-Parkinsonian drugs, for example l-dopa combined with m5Glu or A2A receptor antagonists or l-dopa combined with antagonists of the NMDA or 5-HT2A receptors
Summary
Primary Parkinson syndrome is a progressive neurologial disease. The prevalence among the persons older than 60 years is about 1%. In primary Parkinson syndrome, an altered neurotransmitter balance exists in the basal ganglia with an imbalance between dopaminergic and muscarinic cholinergic systems as well between GABAergic and glutamatergic neurons. Acetylcholine In primary Parkinson syndrome, an altered balance between the dopaminergic and the cholinergic neurotransmitter systems can be found in the basal ganglia. Serotonin Serotonin (5-HT), which mainly exerts an excitatory effect on different serotonin receptors, shows alterations in the basal ganglia in primary Parkinson syndrome [15]. In the section about possible neural pathways in the basal ganglia, it will be pointed out that glutamatergic neurons exert an increased presynaptic effect via NMDA receptors on the dopaminergic neurons placed in the putamen [9]. Substance P-containing neurons in the nucleus caudatus transmit an activating impulse to GABAergic neurons placed in the globus pallidus externus, via NK-1 receptors [9]
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