Norepinephrine uptake sites in the locus coeruleus of rat lines selectively bred for high and low alcohol preference: a quantitative autoradiographic binding study using [3H]-tomoxetine

BACKGROUND: The locus coeruleus (LC) is the largest norepinephrinergic cell group in the central nervous system and contains a high density of norepinephrine (NE) uptake sites. Alcohol-preferring (AP) rats and high-alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, whereas alcohol-nonpreferring (NP) rats and low-alcohol-drinking (LAD) rats are bred for low alcohol preference. However, it is unknown whether NE uptake sites in the LC are associated with alcohol preference in AP and HAD rats when compared with their respective control rats, NP and LAD rats. This study was designed to examine this question. METHODS: Animals were decapitated and brains were removed, frozen with dry ice powder, and stored in a deep freezer. The LC tissue blocks were cut into 14 micro cryostat sections, collected on glass slides, and incubated with 0.6 nM [3H]-tomoxetine in 50 mM Tris-HCl buffer system. For nonspecific binding, 1 microM desipramine was added to the radioactive ligand. Sections were rinsed, quickly dried, and processed for quantitative autoradiography. In addition, galanin content in the LC was also studied. RESULTS: The LC possessed a high density of [3H]-tomoxetine binding sites. There were fewer tomoxetine binding sites (fmol/mg protein) in the AP rats (433.0 +/- 8.1) than in the NP rats (495.6 +/- 3.7). HAD rats (386.5 +/- 13.2) also possessed fewer tomoxetine binding sites than LAD rats (458.7 +/- 10.1). Galanin content in the LC was similar between AP and NP rats and between HAD and LAD rats. CONCLUSIONS: Because both AP rats and HAD rats were selectively bred for alcohol preference, the finding of consistently low levels of [3H]-tomoxetine binding in the LC of these two lines of rats with high alcohol preference suggests that down-regulation of NE transporters in the LC of AP and HAD rats may be associated with alcohol-seeking behavior. A possible involvement of the coerulear NE uptake sites in depression is also discussed. Galanin in the LC may not relate to alcohol preference.     

An early phase II clinical trial of tomoxetine (LY139603) in the treatment of newly admitted depressed patients

In a 6-week open-label study, ten newly admitted depressed patients were treated with tomoxetine, a selective inhibitor of noradrenaline reuptake. After 7 days of drug washout, patients were given an initial dose of 40 mg/day which was gradually increased to a maximum of 70 mg/day (median 50 mg/day). There was a statistically (P<0.001) and clinically significant improvement in the mean symptomatology of the patients measured on the Hamilton Depression Rating Scale. The drug had an early onset of action, a specific effect on mood and no sedative properties.     

托莫西汀治疗儿童注意力缺陷多动障碍研究进展

为探讨托莫西汀对儿童注意力缺陷多动障碍(ADHD)的疗效,本文对托莫西汀治疗儿童ADHD的研究进行综述。通过阐述ADHD发病机制和治疗方案,总结托莫西汀治疗儿童ADHD的效果和安全性,并与哌甲酯、安慰剂治疗的效果进行比较,为ADHD临床治疗提供参考。     

CYP2D6基因多态性与托莫西汀治疗ADHD疗效的关联性研究进展

托莫西汀是目前治疗ADHD的主要药物之一,主要经细胞色素P450酶代谢,是CYP2D6酶的底物。CYP2D6酶具有显著的基因多态性,不同个体CYP2D6酶对托莫西汀代谢能力有所差异,从而影响临床治疗ADHD的效果。查阅近年来国内外相关文献,对CYP2D6基因多态性与托莫西汀治疗ADHD疗效的关联性研究进展进行归纳总结。CYP2D6基因多态性可影响托莫西汀的疗效,CYP2D6慢代谢型患者需要更高的治疗剂量,发生不良反应的风险更高。CYP2D6基因型和表型对托莫西汀体内代谢和临床疗效的影响有待于进一步深入研究,ADHD患者CYP2D6基因多态性分布的全面系统调查也有待于开展,这将有利于托莫西汀治疗ADHD个体化用药的开展。     

哌甲酯及托莫西汀联合脑电生物反馈与单纯脑电生物反馈治疗儿童注意缺陷多动障碍的疗效对比观察

目的 探讨哌甲酯(MPH)及托莫西汀(ATX)联合脑电生物反馈(EEG-B)与单纯EEG-B治疗儿童注意缺陷多动障碍(ADHD)的疗效,为临床治疗提供参考依据。方法 64例ADHD儿童随机分成A、B、C 3组,A组予MPH,B组予ATX,同时联合EEG-B,C组仅予EEG-B,以整合视听持续性操作测试(IVA-CPT)、SNAP-IV问卷为评价工具,比较疗效差异。结果 3组在综合控制力商数和多动/冲动量表得分上均有改善,治疗前后比较差异有统计学意义(均P<0.05);在综合注意力商数和注意力量表得分上均有改善,仅A、B组差异有统计学意义(均P<0.05);两两比较,除多动/冲动量表外,其余结果显示A、B两组差异无统计学意义(均P>0.05),但与C组差异有统计学意义(均P<0.05)。结论 MPH及ATX联合EEG-B可以改善ADHD患儿的核心症状,两者疗效相当,且较单纯的EEG-B治疗更有优势;单纯EEG-B改善ADHD患儿的多动/冲动症状优于注意缺陷症状。     

托莫西汀对哌甲酯治疗无效的注意缺陷多动障碍患儿的疗效和安全性分析

目的:研究托莫西汀对哌甲酯治疗无效的注意缺陷多动障碍(ADHD)患儿的疗效和安全性。方法:对39例经哌甲酯治疗3～6个月无效的ADHD患儿给予托莫西汀治疗8周,分别于第4周和第8周采用Conners父母症状问卷评分评估其疗效和安全性。结果:托莫西汀治疗4周后,26例患儿症状得到缓解;8周后,28例患儿有效;Conners父母症状问卷评分品行、学习、心身障碍、冲动-多动、焦虑因子和多动指数均较治疗前明显降低(P<0.05)。结论:托莫西汀可用于哌甲酯治疗无效的ADHD患儿,其不良反应轻微,可耐受。     

托莫西汀治疗儿童多动症临床疗效分析

目的观察托莫西汀治疗儿童多动症的临床疗效及安全性。方法将58例儿童多动症患者随机分成两组,分别给予托莫西汀与利他林治疗。在治疗前及治疗12周末甩多动指数量表（conners）及治疗副反应量表（TESS）进行评分比较。结果托莫西汀组与利他林组的患者在治疗12周末多动指数总分和行为总分均较治疗前显著降低（P〈0．01）．两组在副反应发生率和严重程度均无显著性差异（P〈0．05）。结论托莫西汀治疗儿童多动症和注意缺陷,疗效确切,安全性好。