Classical Neurotransmitters and Neuropeptides Involved in Parkinson's Disease: Focus on Anti-Parkinsonian Drugs

In Parkinson’s disease a dopaminergic/cholinergic and a GABAergic/ glutaminergic neurotransmitter imbalance occurs in the extrapyramidal system. Here, in this system, we describe the alterations of the classical neurotransmitters dopamine, acetylcholine, serotonin, glutamate and GABA. Dopamine degeneration occurs by oxidative stress and also partly through the function of susceptibility genes. There is an antagonistic interaction between D2 dopaminergic and 5-HT2A serotonergic neurons in the putamen, while serotonin hyperactivity is associated with l-dopa-induced dyskinesia. Nicotinic cholinergic neurons, via ß2 nicotinic cholinergic receptors, activate dopaminergic neurons located in the putamen. 5 metabotropic glutaminergic receptor antagonists could increase dopamine levels through a reduced presynaptic inhibition in the putamen. A2A adenosine antagonists could also have an anti-Parkinsonian effect. A question arises of whether analogues, agonists or antagonists of neuropeptides, such as neurotensin NTS1 antagonists, could be of therapeutic value in the treatment of Parkinson's disease. Neural networks in the extrapyramidal system are also described. Clinical trials should explore the issue of whether a multimodal pharmacotherapy in the treatment of Parkinson's disease is better than a treatment with only dopaminergic drugs.