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While the etiology and pathogenesis of Parkinson's disease (PD) is still obscure, there is evidence for lifestyle factors influencing disease risk. Best established are the inverse associations with smoking and coffee consumption. In other contexts there is evidence that health effects of lifestyle factors may depend on gut microbiome composition. Considering the gastrointestinal involvement in PD, it was recently speculated, that the associations between smoking, coffee, and PD risk could be mediated by gut microbiota. Here we review such a possible mediatory role of gut microbiota taking into account recent findings on microbiome composition in PD and extending the scope also to urate. [ABSTRACT FROM AUTHOR]

The discovery of profound dopamine depletion of basal ganglia in patients with Parkinson's disease and the development of antiparkinsonian drug therapy were largely based on animal models. The behavioural changes caused by cholinergic drugs, reserpine and related agents, and unselective neuronal lesions were the first widely used animal models for Parkinson's disease. The crucial breakthrough was the observation of the circling behaviour in rodents after unilateral intranigral injection of 6-hydroxydopamine. This Ungerstedt model still is one of the basic animal models of Parkinson's disease. It is suitable for the screening of new potential antiparkinsonian agents with the classic spectrum. The parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and the monkey is the latest and the best animal model for Parkinson's disease. Especially when given to the monkey, MPTP causes biochemical, behavioural and neuropathological changes which largely mimick those of Parkinson's disease in man. The MPTP-induced parkinsonism in the monkey can be used for the study of the neurobiology and new forms of drugs therapy of Parkinson's disease. However, because the MPTP monkey model is expensive and laborious, it is not particularly convenient for the screening of new drugs. Recently, a new approach in the treatment of Parkinson's disease is to develop drugs which might prevent or retard the disease progression. The prevention of behavioural changes of aged rodents is used as an animal model and promising results with selegiline have been obtained. [ABSTRACT FROM AUTHOR]

According to investigations, nicotine and its agonists may prevent the development of Parkinson's disease and reduce motor symptoms and dyskinesias in Parkinson's disease. It was shown recently that a transdermal nicotine patch reliefs the symptoms in patients suffering from mild cognitive impairment. In Alzheimer's disease an alpha7-selective agonist has been found to have positive effects on cognitive symptoms. Mutations of nicotinic receptors are underlying certain nocturnal frontal lobe epilepsies. The partial nicotine agonist varenicline may alleviate ataxia symptoms.

Entacapone and tolcapone are reversible COMT inhibitors which have been approved for clinical use in patients with Parkinson disease (PD). Nebicapone is a third COMT inhibitor which has been studied in humans. COMT inhibitors are used in combination with levodopa and a dopa decarboxylase (DDC) inhibitor. Each of them has problems either in pharmacokinetics, pharmacodynamics, clinical efficacy, or in safety. All three inhibitors have short elimination half-lives, about 2-3h. Tolcapone is longer acting and more potent COMT inhibitor than entacapone; nebicapone lies in between. However, none of the present inhibitors cause a complete peripheral COMT inhibition. Tolcapone and nebicapone have increased more levodopa AUC than entacapone which is reflected also in their clinical efficacy. The most common adverse event with COMT inhibitors is dyskinesia which is usually managed by decreasing levodopa dose. The greatest problem with tolcapone and probably also with nebicapone is their liver toxicity which is not seen with entacapone. Tolcapone causes severe diarrhea more often than entacapone. Though the present COMT inhibitors have improved significantly the treatment of advanced PD patients, they still have several problems and weaknesses leaving room for developing better COMT inhibitors., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We tested the possible role of dopaminergic activity in the processing of somatosensory afferent information in healthy humans. Somatosensory evoked magnetic fields (SEFs) were recorded in seven subjects in response to left median nerve stimulation. SEFs were obtained in all subjects after oral administration of 2 mg haloperidol, an antagonist to dopaminergic D2 receptors, and placebo, which were given in a randomized, double-blind cross-over design. SEFs were analyzed using a multiple equivalent current dipole (ECD) model, with one dipole at the right primary somatosensory cortex (SI) and at both left and right secondary somatosensory cortices (SII). The earliest responses from SI, peaking at about 20 ms (N20m) and 35 ms (P35m), were not affected by haloperidol. A later deflection peaking at about 75 ms (P60m), however, was slightly reduced (p < 0.05). Responses arising from SII were not significantly changed. The results suggest that dopaminergic activity may be involved in modulating somatosensory processing after the initial stages of cortical activation.