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771.
CE Beyer Q Lin B Platt J Malberg G Hornby KM Sullivan DL Smith T Lock PJ Mitchell NT Hatzenbuhler DA Evrard BL Harrison R Magolda MN Pangalos LE Schechter S Rosenzweig-Lipson TH Andree 《British journal of pharmacology》2009,157(2):307-319
Background and purpose
As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT1A receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT1A receptor antagonist activities, was evaluated in preclinical models.Experimental approach
Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models.Key results
WAY-211612 inhibited 5-HT reuptake (Ki = 1.5 nmol·L−1; KB = 17.7 nmol·L−1) and exhibited full 5-HT1A receptor antagonist activity (Ki = 1.2 nmol·L−1; KB = 6.3 nmol·L−1; Imax 100% in adenyl cyclase assays; KB = 19.8 nmol·L−1; Imax 100% in GTPγS). WAY-211612 (3 and 30 mg·kg−1, po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT1A receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3–30 mg·kg−1, po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg·kg−1, s.c.) and a 5-HT1A antagonist (WAY-100635; 0.3 mg·kg−1, s.c). WAY-211612 (3.3–30 mg·kg−1, s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3–30 mg·kg−1, i.p. and 10–56 mg·kg−1, po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg·kg−1, i.p.) in the rat scheduled-induced polydipsia model.Conclusions and implications
These findings suggest that WAY-211612 may represent a novel antidepressant. 相似文献772.
773.
Endeshaw YW Ouslander JG Schnelle JF Bliwise DL 《The journals of gerontology. Series A, Biological sciences and medical sciences》2007,62(1):55-61
BACKGROUND: The causes of daytime sleepiness among nursing home residents have not been well recognized. This study examines clinical and polysomnographic factors that are associated with daytime sleepiness among nursing home residents. METHODS: One hundred seventy-four nursing home residents from eight nursing homes in Atlanta, Georgia, participated in the study. Demographic and clinical data were obtained from medical records and assessment of participants obtained by trained research staff. Daytime sleepiness was determined by behavioral sleep-wake observation performed every 15 minutes. Overnight polysomnography was performed in a subgroup of the sample. RESULTS: The mean +/- standard deviation age was 83.4 +/- 8.8 years, and 136 participants were women (78%). The mean percentage +/- standard deviation of behavioral observations with sleep (BOS%) was 19.5 +/- 13.3%. Participants who were able to ambulate independently had significantly lower BOS% (14.2 +/- 9.6 vs 21.2 +/- 6.0, p =.001). Mini-Mental State Examination score was negatively correlated with BOS% (rho = -.279, p =.001). Among 48 participants who had polysomnography, sleep latency, total sleep time, wake after sleep onset, and sleep efficiency were not associated with BOS%. There was a significant negative correlation between BOS% and percentage of time spent in rapid eye movement sleep (rho = -.367, p =.010). Linear regression analyses, with BOS% as the dependent variable, showed that percentage of time spent in rapid eye movement sleep was the only variable independently predicting BOS%. CONCLUSION: Absence of association between BOS% and nocturnal sleep suggests that the causes of daytime sleepiness and nocturnal sleep problems may not be related. This finding may have important implications for interventions that aim to reduce daytime sleepiness among nursing home residents. 相似文献
774.
Personality traits and psychological reactions to mental stress of female migraine patients 总被引:5,自引:0,他引:5
DL Stronks JHM Tulen L Pepplinkhuizen R Verheij GWH Mantel P Spinhoven J Passchier 《Cephalalgia : an international journal of headache》1999,19(6):566-574
The purpose of this study was (i) to compare a range of stress-related personality traits, including defense and coping mechanisms, of migraine patients (n = 23) with those of tension headache patients (n = 18) and dermatologically afflicted, but otherwise healthy, controls (n = 22), and (ii) to compare their state anxiety and other moods before, during, and after the presentation of a psychological stressor (mental arithmetic). For all three groups, mental arithmetic induced a significant increase in state anxiety and mood disturbance, followed by a subsequent decrease during recovery. Migraine patients were not found to have a higher disposition for anxiety, depression, or rigidity than tension headache patients or controls. Between the headache groups no differences in the use of defense and coping mechanisms were found. Compared to the control group, however, both migraine patients and tension headache patients were more inclined to use internally focused defense mechanisms and less inclined to seek social support when confronted with a problem. The psychological reaction of migraine patients to mental stress hardly differed from tension headache and control subjects. Compared to the control subjects, however, both groups of headache patients exhibited a diminished recovery from feelings of vigour, depression, and fatigue due to the stress induced. It is suggested that this distinct psychological reaction to stress of headache patients versus healthy control subjects is related to the more internally focused defense style of the headache sufferers. Thus, in contrast to previous results, this study does not present evidence of a migraine personality. It suggests the development of specific personality characteristics as a consequence of suffering from episodic headache. 相似文献
775.