抗抑郁剂吗氯贝胺的行为效应

加强5-羟色氨酸及β-苯乙胺致小鼠刻板行为实验表明, ig吗氯贝胺(Moc)对单胺氧化酶(MAO)- A 的选择性抑制作用 (ED₅₀=0.33 mg·kg^-1, 2 h) 较MAO-B (ED₅₀=12.7 mg·kg^-1, 2 h) 强约39倍. 24 h内ip Moc 300 mg·kg^-1有一定镇静作用. 对运动系统无明显影响，不引起记忆及定向障碍. Moc 600 mg·kg^-1不能对抗氧化震颤素引起的小鼠震颤和分泌增加. Moc的LD₅₀为小鼠: 1.3-1.5 g·kg^-1 ig; 198-199 mg·kg^-1 iv; 大鼠: 541-562 mg·kg^-1 ip. Moc 剂量依赖地对抗利血平引起的小鼠和大鼠睑下垂, 活动减少和体温降低；使慢性应激刺激引起的小鼠活动性增高及穿箱逃避电击反应失败率增高得到恢复，提示其抗抑郁作用.     

吗氯贝胺在鼠强迫游泳行为实验中的抗抑郁效应

用大鼠和小鼠强迫游泳行为模型观察了吗氯贝胺的抗抑郁效应。大鼠一次给予吗氯贝胺１０－１００ｍｇ·ｋｇ￣（－１）无影响。２４ｈ内３次强化给药使游泳不动时间减少。若每日给药２次。连续１５次则不但效应进一步加强且呈较好的量效关系，同时活动性不增加。小鼠单次或３次强化给予吗氯贝胺对游泳不动时间均无明显影响。每日１次。连续给药２０ｄ，表现出与大鼠同样的良好效应和量效关系。活动性亦无增高。     

吗氯贝胺的临床应用

吗氯贝胺是一种可逆性选择性单胺氧化酶A抑制剂 ,对抑郁症 (不同亚型 )的疗效肯定 ,与三环类 (或一些杂环类药物 )和 5 羟色胺再摄取抑制剂相当。吗氯贝胺有效治疗量为 30 0～ 6 0 0mg·d- 1,分 2～ 3次服用。另外吗氯贝胺对社交恐惧症、惊恐障碍的疗效与氟西汀和氯米帕明相当。吗氯贝胺的不良反应最常见的是恶心和失眠。在治疗剂量 ,吗氯贝胺对精神运动性表现、认知功能和心血管系统没有显著不良反应。其耐受性好。吗氯贝胺的剂量在小于 90 0mg·d- 1时 ,不必考虑饮食限制。吗氯贝胺是CYP2C19的底物 ,其血浆T1/2 短 ,在 2 4h内可换用其他药物。     

新型抗抑郁药—吗氯贝胺

新型抗抑郁药──吗氯贝胺高家荣（安徽中医学院附属医院合肥２３００３１）吗氯贝胺（Ｍｏｃｌｏｂｅｍｉｄｅ）是一特异性单胺氧化酶Ａ（ＭＡＯ－Ａ）可逆性抑制剂，能治疗多种抑郁症，且具有时效关系，也能降低抗胆碱能的副作用。吗氯贝胺是苯甲酰胺的衍生物，本品于１...     

吗氯贝胺的合成

以对氯苯甲酸为原料,酯化后在NH4Cl催化下与乙醇胺反应生成N-(2-羟乙基)对氯苯甲酰胺,再与氯化亚砜反应生成N-(2-氯乙基)对氯苯甲酰胺,最后与吗啉缩合制得吗氯贝胺,总收率42.6%.     

HPLC法测定吗氯贝胺片含量

目的　建立了一种测定吗氯贝胺的HPLC新方法。方法　在室温下以甲醇∶水(30∶70 )为流动相,检测波长为2 4 0nm,流速为 1 0ml·min-1。结果　吗氯贝胺在 2 5～ 80 μg·ml-1范围内呈良好线性,最低检测限为 3 0ng,回收率为 98 9～10 0 2 %。结论　本法简便,准确,重现性好,可用于本制剂的含量测定及质量控制     

吗氯贝胺的合成

以对氯苯甲酰氯为起始原料，与Ｎ－（２－氨乙基）吗啉综合制得吗氯贝胺，收率：７４．５％。     

吗氯贝胺的大鼠致畸试验

吗氯贝胺的大鼠致畸试验高晓奇王蕊李厚勇吗氯贝胺是一种新的可逆的选择性单胺氧化酶亚型Ａ抑制剂，临床用于治疗重度抑郁症。材料与方法一、吗氯贝胺纯品（９９％）山东省医药工业研究所提供。ＬＤ５０为７０７ｍｇ／ｋｇ。二、实验动物为Ｗｉｓｔａｒ大鼠，体重２５０～...     

HPLC法测定吗氯贝胺片的含量

建立了测定片剂中吗氯贝胺的ＨＰＬＣ方法，色谱条件为ＷａｔｅｒｓＣ１８色谱柱，乙腈－０．０５ｍｏｌ／Ｌ醋酸铵溶液－冰醋酸（２５：７５：１．５）为流动相，２５４ｎｍ检测波长，咖啡因为内标，该法简便，灵敏，准确，吗氯贝胺在１９．８～１９８．０ｍｇ／Ｌ浓度内线性关系良好（ｒ＝０．９９９９），平均回收率为１００．０％，（ＲＳＤ＝０．１７％，ｎ＝５）。     

国产吗氯贝胺的抗抑郁作用

研究国产吗氯贝胺对抑郁动物模型和单胺氧化酶－Ａ（ＭＡＯ－Ａ）活性的影响。吗氯贝胺５、１０、２０ｍｇ·ｋｇ－１（ｉｇ）可显著对抗利血平（２．８ｍｇ·ｋｇ－１，ｓｃ）引起的大鼠眼睑下垂，其抑制率分别为６０％，８０％与９０％。在小鼠获得性“绝望”实验中，吗氯贝胺５，１５，２５ｍｇ·ｋｇ－１（ｉｇ）可明显缩短小鼠６ｍｉｎ内不动时间。本研究尚证实，吗氯贝胺６，１２，２４ｍｇ·ｋｇ－１（ｉｇ）可抑制小鼠脑组织中ＭＡＯ－Ａ活性，并与剂量呈明显依赖关系。一次给予小鼠２４ｍｇ·ｋｇ－１（ｉｇ），２ｈ后吗氯贝胺对ＭＡＯ－Ａ活性的抑制作用达高峰（７４．７％），４ｈ后ＭＡＯ－Ａ活性开始有所恢复，于用药后１６ｈ活性已基本趋于正常。     

氟西汀与米安色林对小鼠自主活动,探究和攻击行为药理作用的比较

观察和比较氟西汀与米安色林对小鼠自主活动 ,探究和隔离攻击行为的影响 ,探讨二者可能的药理学作用差异 .研究采用以下方法 :①测定群居小鼠的自主活动性和探究行为 ;②评价隔离饲养 4 8～5 7d小鼠的攻击行为 .结果显示 :①ip氟西汀 2 .5～10mg·kg- 1对隔离小鼠的攻击行为具有完全的拮抗作用 ,但对小鼠的自主活动和探究行为无明显影响 ;②ip米安色林 0 .5 ,2 .5或 5mg·kg- 1呈剂量依赖性抑制隔离小鼠的攻击行为 ,并明显减少小鼠的自主活动和探究行为 .结果说明 ,氟西汀和米安舍林对小鼠的自主活动 ,探究行为以及隔离攻击行为的影响并不完全一致 ,可能与它们不同的药理学作用机理有关 .     

Sleep-endocrine profile of the antidepressant mianserin

Summary

The effects of mianserin, a tetracyclic antidepressant, on sleep stages and on the nocturnal secretion of cortisol, ACTH, growth hormone, prolactin and tryptophan were studied on II normal male volunteers in a double-blind, placebo-controlled study. Mianserin increased Stage 3 time (p <0.001) and Stage 4 time (p <0.01). It reduced the number of REM periods (p <0.001), the REM latency after sleep onset (p <0.01) and both the total and percentage REM time (p <0.05). A reduction in both the total sleep time (p <0.05) and the percentage of total time in bed (p <0.05) were the only significant carry-over effects from the drug treatment period. No significant difference in any biochemical measurement was found between placebo and drug treatment.     

A review of the reversible MAO-A inhibitor moclobemide in geriatric patients

At present, in Western Europe and the USA 12–15 per cent of the total population are over 65 years old. The portion of mentally abnormal persons in this age group is given at 30 per cent. After dementing disorders, depressive syndromes are the most frequent psychiatric diseases of old age. In the use of antidepressant, psychoactive drugs, one should bear in mind age-related pharmacokinetics and pharmacodynamic changes, frequently present multimorbidity, poor compliance, and drug side effects or interactions as complicating factors. In this report the reversible MAO-A inhibitor, moclobemide, which has now been in clinical use for about 5 years, is examined critically with respect to its pharmacological mode of action, its pharmacokinetic profile, and its tolerability, especially from the psychogeriatric aspect which has received little attention to date. A comparison of the relevant literature shows that moclobemide has advantages over other, classic, antidepressants because of better tolerability, fewer side effects and interactions, shorter latency of effect, and lower toxicity. These advantages, together with a favourable influence on cognitive capacities appear to be very useful, particularly in old age. At this point, however, a conclusive judgment still cannot be reached. Further controlled studies are required for this purpose. © 1998 John Wiley & Sons, Ltd.     

Blood pressure effects of monoamine oxidase inhibitors in response to orally administered tyramine in the rat

The reversible monoamine oxidase-A inhibitors BW 1370U87, BW 616U76, brofaromine, and moclobemide, and the irreversible nonselective monoamine oxidase inhibitor phenelzine were compared for potentiation of the pressor response to oral tyramine. Conscious rats were pretreated with doses of the monoamine oxidase inhibitors sufficient to produce 80% inhibition of brain monoamine oxidase, and then were challenged with orally administered tyramine. Blood pressure was monitored prior to and after tyramine, and peak pressor responses were compared. At a dose of 15 mg/kg tyramine, the pressor response of BW 1370U87 was statistically similar to the vehicle control response. BW 616U76, brofaromine, and moclobemide elicited mild tyramine pressor effects, whereas phenelzine resulted in a marked elevation of blood pressure. Higher doses of tyramine elicited blood pressure elevations from all of the monoamine oxidase inhibitors.     

Do adrenergically active drugs have a role in the first-line treatment of attention-deficit/hyperactivity disorder?

Adrenergically active drugs used for the treatment of attention-deficit/hyperactivity disorder (ADHD) include the α-agonists, monoamine oxidase inhibitors, tricyclics and the selective noradrenergic re-uptake inhibitors. In addition to a longer duration of treatment effect than the predominantly dopaminergic psychostimulant drugs, a theoretical advantage of the adrenergically active drugs is a lesser tendency to aggravate common comorbidities of ADHD, such as anxiety, obsessionality, depression and tics. Nevertheless, adrenergically active drugs have always been considered second-line treatments to the psychostimulant drugs. No study has demonstrated superiority of adrenergically active drugs over the psychostimulants in reducing the core symptoms of ADHD, although several small trials have suggested ‘equivalence’. The case for superiority of the adrenergically active drugs over psychostimulants in alleviating comorbid symptoms remains largely unproven, as there have been few comparative trials. Safety data have favoured the psychostimulant drugs. The advantage of once daily or morning and evening dosing of the adrenergically active drugs has been diminished since the introduction of sustained release preparations of methylphenidate and amphetamine. Although adrenergically active drugs may be the preferred treatment in the presence of severe comorbidity, for the most part they remain second-line treatment for ADHD.     

小补心汤总黄酮对强迫游泳和获得性无助模型动物的抗抑郁作用(英文)

目的小补心汤(XBXT)由代赭石、旋覆花、竹叶和淡豆豉4味中药组成,文献记载其有缓解抑郁情绪的作用。本实验研究其总黄酮提取物(XBXT-2)是否具有抗抑郁作用。方法采用大、小鼠强迫游泳模型和大鼠获得性无助模型观察XBXT-2的抗抑郁作用,采用酶联免疫法检测获得性无助大鼠血清皮质酮水平,并观察XBXT-2对小鼠自发活动的影响。结果单次灌胃给予XBXT-2 50和100mg.kg-1可以显著缩短小鼠和大鼠强迫游泳的不动时间。连续4 d灌胃给予XBXT-2 25和50 mg.kg-1可以显著减少获得性无助模型大鼠的逃避失败次数,并显著降低其血清皮质酮水平。XBXT-2 50 ～200 mg.kg-1对正常小鼠的自发活动性无明显影响。结论 XBXT-2在抑郁动物模型上具有抗抑郁样作用,其机制可能与其抑制下丘脑-垂体-肾上腺轴功能亢进有关。