A Phase 1, Multiple Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Examining the Effects of CXB722 in Mitigating Neuroendocrine Stress Response in Healthy Males

The purpose of this study is to assess the effects of CXB722 on neuroendocrine stress response and subjective reports related to mood and stress during and after experimentally induced stress among healthy young males.

开始日期2008-12-01

申办/合作机构

CeNeRx BioPharma, Inc.

100 项与 Pivagabine 相关的临床结果

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100 项与 Pivagabine 相关的转化医学

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100 项与 Pivagabine 相关的专利（医药）

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项与 Pivagabine 相关的文献（医药）

2001-07-01·Behavioural Brain Research3区 · 心理学

Pivagabine effects on neuroendocrine responses to experimentally-induced psychological stress in humans

3区 · 心理学

Article

作者: G. Gerra ; R. Delsignore ; A. Zaimovic ; F. Giusti ; F. Brambilla ; M.C. Baroni ; M.A. Raggi

Neuroendocrinology of chronic stress seems to be characterized by HPA axis hyperactivity and early childhood stressors have been hypothesized to predispose individuals to adult onset depression by means of dysregulation of the HPA axis. Pivagabine (PVG), a hydrophobic 4-aminobutyric acid derivative, has been used experimentally recently in the treatment of different disorders related to stress-maladaptation, because of its possible inhibitory action on corticotrophin releasing factor secretion and HPA axis function. In the present study, 20 healthy male subjects were each exposed twice to the same psychosocial stressor (stroop color-word interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT), heart rate (HR) and systolic blood pressure (SBP) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. Utilizing a double blind schedule, the subjects received pivagabine (900 mg, twice a day)(PVG group: nine subjects) or placebo (PBO group: 11 subjects) during the 7 days between the two stress sessions. NE, EPI, ACTH, and CORT levels were significantly elevated after stress exposure on day 1 and day 8 in PBO group subjects. After PVG treatment, on day 8, ACTH, CORT, NE and EPI responses to stress were significantly blunted, together with HR and SBP, in PVG group subjects. These results add to the evidence concerning PVG capacity to inhibit the HPA axis in humans, in response to stressful stimuli, and suggest that the action of PVG may be mediated not only by GABAergic receptors, but also by the suppression of catecholamines response. PVG treatment could modulate HPA hyper-responsiveness to stress in subjects with negative affectivity and depressive traits.

2000-12-01·Molecular Brain Research

Pivagabine-induced increases in the abundance of CRF mRNA in the cerebral cortex and hypothalamus of rats

Article

作者: Paolo Follesa ; Giovanni Biggio ; Stefania Porta ; Gaetano Espositoto ; Elisabetta Cagetti

The effect of treatment of rats with pivagabine (4-[(2,2-dimethyl-1-oxopropyl) amino] butanoic acid) for 4 days on the abundance of corticotropin-releasing factor (CRF) mRNA in the brain was investigated. Such treatment resulted in dose-dependent (100-300 mg/kg, i.p.) increases in the amount of CRF mRNA in both the hypothalamus and cerebral cortex. The maximal increases were thus apparent with the dose of 300 mg/kg in the hypothalamus (+108%) and cerebral cortex (+49%) 30 or 60 min, respectively, after the last drug injection. Foot-shock stress administered 30 min after the final drug injection had no effect on the pivagabine-induced increases in the abundance of CRF mRNA in the hypothalamus or cerebral cortex. Such stress also had no effect on the amounts of CRF mRNA in these brain regions of vehicle-treated rats. These results demonstrate that pivagabine increases the amount of CRF mRNA in both the hypothalamus and cerebral cortex of rats, effects that might be relevant to the action of this drug in preventing the stress-induced changes in CRF hypothalamic concentration.

2000-09-01·Journal of Endocrinological Investigation2区 · 医学

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea

2区 · 医学

Article

作者: Ar Genazzani ; M Fedalti ; Ad Genazzani ; M Santuz ; Felice Petraglia ; M Stomati ; Stefano Luisi ; C Bersi ; G Esposito

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

100 项与 Pivagabine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D07342	Pivagabine	N06AX15	DB12951

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
焦虑症	临床2期	美国	CeNeRx BioPharma, Inc.	-
焦虑症	临床2期	-	CeNeRx BioPharma, Inc.	-
抑郁症	临床2期	美国	CeNeRx BioPharma, Inc.	-
心理压力	临床2期	美国	CeNeRx BioPharma, Inc.	-