CNS neuroscience & therapeutics
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The diagnosis of Parkinson disease (PD) is rendered on the basis of clinical parameters, whereby laboratory chemical tests or morphological imaging is only called upon to exclude other neurodegenerative diseases. The differentiation between PD and other diseases of the basal ganglia, especially the postsynaptic Parkinson syndromes multisystem atrophy (MSA) and progressive supranuclear palsy (PSP), is of decisive importance, on the one hand, for the response to an appropriate therapy, and on the other hand, for the respective prognosis of the disease. However, particularly at the onset of symptoms, it is difficult to precisely distinguish these diseases from each other, presenting with an akinetic-rigid syndrome. ⋯ Therefore, a reliable biomarker is still to be found that might predict the development of Parkinson dementia. Since this situation is currently the subject of various different studies, the following synopsis is intended to provide a brief summary of the investigations addressing the field of the early neurochemical differential diagnosis of Parkinson syndromes and the early diagnosis of Parkinson dementia, from direct alpha-synuclein detection to proteomic approaches. In addition, an overview of the tested biomarkers will be given with regard to their possible introduction as a screening method.
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Vilazodone (EMD 68843; 5-{4-[4-(5-cyano-3-indolyl)-butyl]-1-piperazinyl}-benzofuran-2-carboxamide hydrochloride) is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist currently under clinical evaluation for the treatment of major depression. This molecule was designed based on the premise that negative feedback circuitry, mediated via 5-HT1 receptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. If the hypothesis is correct, combination of SSRI with 5-HT1A partial agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. ⋯ In the forced swim test (a putative model of depression), vilazodone also showed efficacy but at a single dose only. In man, vilazodone abolished REM sleep and demonstrated clinical antidepressant efficacy equivalent to an SSRI. Ongoing clinical evaluations will hopefully reveal whether the founding hypothesis was valid and if vilazodone will produce a more rapid onset of antidepressant efficacy.