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Background: The prevalence of smoking in patients with schizophrenia is higher than that in the general population and is an important medical issue. Short-term smoking cessation tends to worsen psychiatric symptoms in patients with schizophrenia but decreases sympathetic nervous system activity and improves plasma cholesterol levels in healthy people. Few studies have assessed the long-term effects of smoking cessation in patients with schizophrenia. Methods: Subjects were 70 Japanese patients with schizophrenia (38 smokers, 32 non-smokers). We compared the following clinical parameters between the two groups at baseline (before smoking cessation) and in each group separately between baseline and at three years after smoking cessation: autonomic nervous system activity, plasma cholesterol levels, body weight, drug therapy, and Global Assessment of Functioning scores. We also compared the mean changes in clinical parameters throughout this study between the groups at both time points. Autonomic nervous system activity was assessed by power spectral analysis of heart rate variability. Results: Parasympathetic nervous system activity and the doses of antiparkinsonian drugs in smokers were significantly higher than those in non-smokers at baseline. Smoking cessation was associated with significantly decreased sympathetic nervous system activity and decreased doses of antipsychotics and antiparkinsonian drugs at three years after smoking cessation. However, there was no significant difference in the mean change in clinical factors scores, except for Global Assessment of Functioning scores, between smokers and non-smokers at three years after smoking cessation. Conclusions: Our results suggest that smoking reduces both autonomic nervous system activity and the effectiveness of drug therapy with antipsychotics and antiparkinsonian drugs in patients with schizophrenia, but that both factors could be ameliorated over the long term by smoking cessation. Taken together with the findings of previous studies, smoking cessation in patients with schizophrenia has many long-term positive physiological effects. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a major worldwide public health problem with a prevalence that is expected to increase dramatically in the coming decades. Because administrative data are useful for epidemiologic and health service studies, we aimed to define procedural algorithms to identify PD patients (on a regional basis) using these data. We built two a priori algorithms, respecting privacy laws, with increasing theoretical specificity for PD including: (1) a hospital discharge diagnosis of PD; (2) PD-specific exemption; (3) a minimum of two separate prescriptions of an antiparkinsonian drug. The two algorithms differed for drugs included. Sensitivities were tested on an opportunistic sample of 319 PD patients from the databases of 5 regional movement disorders clinics. The estimated prevalence of PD in the sample population from Tuscany was 0.49 % for algorithm 1 and 0.28 % for algorithm 2. Algorithm 1 correctly identified 291 PD patients (sensitivity 91.2 %), and algorithm 2 identified 242 PD patients (sensitivity 75.9 %). We developed two reproducible algorithms demonstrating increasing theoretical specificity with good sensitivity in identifying PD patients based on an evaluation of administrative data. This may represent a low-cost strategy to reliably follow up a large number of PD patients as a whole for evaluating the effects of therapies, disease progression and prevalence. [ABSTRACT FROM AUTHOR]

Using molecular simulations, we study the adsorption and diffusion of an antiparkinsonian drug known as amantadine (or 1-aminoadamantane) in different single-walled carbon nanotubes (SWCNs) with diameters ranging from 10.9 to 27.1 Å. First, we compute the adsorption isotherm for each SWCN atusing the recently developed expanded Wang–Landau (EWL) simulations. This method allows for a direct computation of the grand canonical partition function of the system studied which, in turn, gives access to thermodynamics properties important for the adsorption process. The EWL approach is especially well suited to study the adsorption of large molecules in nanoporous materials since it combines the advantages of the expanded ensemble, in which the insertion and deletion of molecules is divided into a large number of steps, and of the Wang–Landau sampling scheme, which ensures uniform sampling of the number of molecules adsorbed in the porous material. Second, to characterise transport in these systems, we use molecular dynamics simulations to determine how self-diffusivity varies with the loading in amantadine. This allows us to shed light on the interplay between structure and transport in the nanoconfined fluid. In particular, we identify a sharp change in the rate at which the self-diffusivity decreases with the loading and relate it to a transition of the confined fluid from a single cylindrical layer to a bilayer, when additional adamantine molecules are adsorbed in the central region of the pore. [ABSTRACT FROM PUBLISHER]

The authors review management issues in Parkinson's disease (PD) and provide an overview of the current pharmacological management strategies, with a specific focus on safinamide. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using levodopa, dopamine agonists, and inhibitors of dopamine-metabolizing enzymes. Currently under investigation for use in the treatment of PD, safinamide has multiple modes of action including monoamine oxidase B inhibition. It is well absorbed orally, has a long plasma half-life, and does not have liver enzyme-inducing or liver enzyme-inhibiting activity. Peak plasma concentration occurs 2-4 hours after single oral doses. Safinamide as monotherapy and as an adjunct to dopamine agonists improves Unified Parkinson's Disease Rating Scale motor scores. One randomized, placebo-controlled trial involving 168 patients given a median safinamide dose of 70 mg/day (range 40-90 mg/day) significantly increased the proportion of responders - defined as patients improving their Unified Parkinson's Disease Rating Scale motor scores by 30% or more from baseline - after 3 months (37.5% for safinamide versus 21.4% for placebo; P < 0.05). Safinamide increased "on" time with no or minor dyskinesia compared with the placebo in another trial, but dyskinesia severity was not reduced. Safinamide was well tolerated, with an adverse effect profile similar to that of the placebo. Further Phase III trial data for safinamide efficacy is awaited, and will be of interest in a comparison with other developments in PD therapeutics: modified formulations of available compounds, new drug classes such as adenosine receptor antagonists, and gene-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: In order to investigate the functional interaction between the native dopamine receptors and their coupled guanine nucleotide-binding regulatory (G) proteins, dopamine-stimulated [35S]guanosine 5′-O-(γ-thiotriphosphate) ([35S]GTPγS) binding was pharmacologically characterized in rat striatal membranes. Following optimizing the experimental conditions as to the concentrations of GDP, MgCl2 and NaCl in the assay medium, the agonist and antagonist properties for a series of dopamine receptor ligands were determined mainly under the standard assay condition. The pharmacological profile of this response clearly indicated the involvement of dopamine D2-like receptors, but not of dopamine D1-like receptors. Among the types of dopamine D2-like receptors, dopamine D2 receptors most likely appeared to be involved in dopamine-stimulated [35S]GTPγS binding in rat striatal membranes, because the affinities of agonists and antagonists determined in the present study were significantly correlated with those reported in the previous literature only for dopamine D2 receptors, but not for dopamine D3 or D4 types. Though the concentration-dependent inhibition curves of dopamine-stimulated [35S]GTPγS binding by spiperone and S(−)-raclopride were apparently biphasic, the origin of the low-affinity minor components was not fully determined. The antiparkinsonian drugs with the properties of dopamine receptor agonism were shown to behave as stimulants with varied affinities and relative efficacies in the current assay system. On the other hand, neither phencyclidine (PCP) nor ketamine stimulated the specific [35S]GTPγS binding, in contrast with the previous report demonstrating that these two N-methyl-d-aspartic acid (NMDA) receptor antagonists behaved as agonists at human dopamine D2 receptors expressed in Chinese hamster ovary (CHO) cells. These results provide important information about the functional activation of G proteins coupled with dopamine D2 receptors as well as agonist actions of various compounds at native dopamine D2 receptors, which are potentially involved in pathophysiology and pharmacotherapy of neuropsychiatric diseases such as Parkinson''s disease, schizophrenia and depression. [Copyright &y& Elsevier]

Summary Objective: Marked interpatient variability in haloperidol (HAL) level–dose (L/D) ratios makes it difficult to use the administered dose for predicting serum concentrations. Objective: To investigate the effect of dose, age, total body weight and co-medication on steady-state HAL L/D ratios. Method: Retrospective analysis of dose and HAL blood level data from 168 patients. Results: The HAL L/D ratio decreased curvilinearly with increasing daily dose of HAL. The patients treated with concomitant antiparkinsonian drugs showed a mean HAL L/D ratio that was 24·9% higher than those without antiparkinsonian drugs. The patients treated with concomitant antiepileptic drugs showed a mean HAL L/D ratio that was 27·2% lower than those without antiepileptic drugs. The mean HAL L/D ratio of patients treated with concomitant CYP2D6 substrates was not significantly different from those without CYP2D6 substrates. Conclusion: There is a wide interindividual variability in blood levels of HAL in patients given the same dose. Routine monitoring of HAL serum level is useful, especially in patients who require associated antiepileptic and/or antiparkinsonian medication. [ABSTRACT FROM AUTHOR]