Long-term use of flupirtine leads to withdrawal symptoms and is associated with dependency.

This is the case of a 44-year-old woman, who was treated as an inpatient because of withdrawal symptoms like sweating, tremors, sleeping disorders and irritability after long-term use of flupirtine. She recovered by symptom-based application of pipamperone within 72 h after flupirtine cessation.

Changes in gustatory perceptions of patients with major depression treated with vagus nerve stimulation (VNS).

BACKGROUND: Olfactory and gustatory functions were investigated before and during vagus nerve stimulation (VNS) in a group of 9 patients with therapy-resistant depression, implanted with a VNS system. METHODS: Gustation and olfaction were tested using standard sniffing tests. Subjects participated in 2 sessions with the vagal stimulator switched on and off, respectively. RESULTS: Under conditions of stimulation of the VNS, there were statistically significant differences of the threshold of perception, with an intensification of the taste "sweet" (Z = -2.0; p = 0.048) and "bitter" (Z = - 2.5; p = 0.011) compared to the "off-mode". A statistical trend (Z = - 1.7; p=0.098) for increased intensity of the taste "salty" was observed, however, these results would supposedly disappear after correction for multiple testing presumably due to the large number of variables and the small sample size. There were no statistically relevant differences concerning olfactory perception. CONCLUSIONS: The changes of gustatory perception under conditions of vagal nerve stimulation observed in this study show another important central nervous effect of vagal stimulation on the limbic system that might be of importance in the elucidation of mechanisms of action of VNS especially on refractory depression.

The P300 event-related potential and smoking--a population-based case-control study.

A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case-control study N=1318 participants (smokers and never-smoking controls) were investigated at 6 German academic institutions. Study participants were randomly selected from the general population. Subjects with mental disorders including alcoholism and drug abuse were excluded. The main outcome measure was the P300 global field power (GFP). We found a lower P300 GFP in current smokers compared to never-smoking controls. Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found. Non-addicted smokers exhibited normal P300 ERP measures. This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity. Thus, P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers. Our results provide the phenotypical groundwork for future multidimensional analyses of genotype-phenotype relationships in the field of smoking and nicotine dependence.

Memantine fails to facilitate partial cigarette deprivation in smokers--no role of Memantine in the treatment of nicotine dependency?

The efficacy of Memantine in the treatment of nicotine dependency in humans remained to be evaluated. The aims of our pilot study were to investigate (1) the effectiveness of Memantine in facilitating smoking reduction and (2) the influence of Memantine on the perception of nicotine. In order to achieve these aims we conducted a placebo controlled double-blind parallel group study in smokers (n = 20 per group). Before the beginning of the treatment-phase (10/20 mg Memantine per day) all participants were instructed to reduce smoking (partial deprivation). Before and during partial deprivation we registered the daily cigarette consumption and craving estimates. Following nasal stimulation with nicotine enantiomers hedonic and intensity estimates and the discrimination ability were assessed. Memantine failed to facilitate smoking reduction and did not influence the perception of nicotine with the exception of a weak reduction of olfactory intensity estimates reaching statistical significance for one nicotine enantiomer only.

Specific sensory detection, discrimination, and hedonic estimation of nicotine enantiomers in smokers and nonsmokers: are there limitations in replacing the sensory components of nicotine?

The aim of this study was to investigate in smokers and nonsmokers (1) the olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the discrimination ability and hedonic estimation of nicotine enantiomers in olfactory and trigeminal concentrations. Thirty healthy male subjects (15 smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli) were introduced into the right nostril of the subjects using a Kobal-olfactometer. The subjects were instructed to group the stimuli into two categories (A and B). To test the role of the olfactory and the trigeminal system in this discrimination task, the authors studied the olfactory detection threshold for the "odorous" sensation and the trigeminal detection thresholds for the "burning" and "stinging" sensations. Nicotine enantiomers were presented at the individual "olfactory" and "trigeminal" concentration levels. The subjects estimated the hedonic properties using a bipolar visual analog scale (from "very unpleasant" to "very pleasant"). A statistical evaluation (t-test) revealed that the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and trigeminal concentrations (p < or = 0.01, p < or = 0.001, respectively). At concentrations near the detection thresholds, i.e., clearly below subjective pain thresholds, smokers rated both nicotine stereoisomers to be significantly more pleasant than did nonsmokers (t-test, R(+)-nicotine: p < or = 0.05; S(-)-nicotine: p < or = 0.01). Increasing the concentrations to above trigeminal thresholds resulted in a difference in hedonic estimates. Smokers perceived the S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations (t-test, p < or = 0.001). This difference in perception might be explained by the smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer in tobacco.

Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man.

RATIONALE: Nicotine applied to the nasal cavity can evoke 'odorous' sensations in the concentration range near the detection threshold by the activation of the olfactory sensory system and at higher concentrations 'burning' and 'stinging' sensations by the dose-dependent recruitment of C- and Adelta-fibers of the trigeminal sensory system. Neuronal nicotinic acetylcholine receptor (nAchR) subunits are expressed in trigeminal primary afferents and could constitute the receptors involved in nicotine perception. OBJECTIVE: In the present study, we dose-dependently investigated the stereoselective effects of R(+)- and S(-)-nicotine on the trigeminal and olfactory sensory system in man. METHODS: Trigeminal detection thresholds for the 'burning' and 'stinging' sensations and the olfactory detection threshold for the 'odorous' sensation were determined. In order to quantify trigeminal activation, we recorded summated electrical responses from the respiratory nasal mucosa during stimulation with R(+)-and S(-)-nicotine vapor (40, 80, 120, 160 ng/ml; stimulus duration: 250 ms). In addition, subjects rated the intensity of 'odorous', 'burning' and 'stinging' sensations. For chemical stimulation with nicotine enantiomers, a vapor-dilution olfactometer (constant flow rate: 140 ml/s, humidity: 80%, temperature: 37 degrees C, stimulus duration 250 ms) was employed. RESULTS: We found significant stereoselective differences for the trigeminal but not for the olfactory system, i.e. higher summated responses, higher trigeminal intensity estimates, and lower trigeminal detection thresholds for S(-)- compared to R(+)-nicotine. CONCLUSION: Our results clearly demonstrate the different stereoselective activation of the trigeminal sensory system by R(+)-and S(-)-nicotine, indicating the presence of specific stereoselective receptors on trigeminal nociceptive Adelta- and C-fibers.