英文药名: Provigil(Modafinil Tablets)

中文药名: 莫达非尼片,莫待芬宁,莫达非尼,普卫醒锭,聪明药

药物名称

【通用名称】 莫达非尼片
【英文名称】 Modafinil
【英文别名】 2-[(Diphenylmethyl)sulfinyl]-acetamide
【化学名称】 2-[（二苯基甲基）亚硫酰基]乙酰胺
【性　　状】 本品为白色或类白色的结晶性粉末；无臭、几乎无味。本中种在甲醇中略溶，在乙醇或乙酸乙酯中微溶，在水中几乎不溶。
药物简介

本品已经获得20多个国家的批准，其商品名有Provigil、Alertec、Modiodal、Modasomil、Modavigil和Vigil等。
2004年，美国FDA批准了本品（Provigil）在轮班工作睡眠障碍和阻塞性睡眠呼吸暂停综合征所致过度嗜睡的患者中用于改善失眠症。FDA于1998年批准本品在发作性睡病所致过度嗜睡的患者中用于改善失眠症。
Provigil被用于有发作性睡病、阻塞性睡眠呼吸暂停综合征/低通气综合征和轮班工作睡眠疾病的成人患者，特别被用于因特殊需要长时间连续工作的人。它可使人保持清醒的头脑，因而被戏谑为“不夜神”。
适应症

抑郁症患者。特发性嗜睡或发作性睡眠症。
用法用量

口服。每日睡前1.5小时服50～100mg，每4～5天增加50毫克，直至最适剂量（每日200～400毫克）
任何疑问，请遵医嘱！
不良反应

该药在世界范围内已出现若干严重或威胁生命的皮疹报告，包括中毒性表皮坏死松解症型药疹等。
医师应告诫病人，如果出现皮疹应立即停止使用本品，并迅速就诊。医师和消费者还应该明白，本品不能被用于儿科患者的任何适应症。
另外也有用了Provigil的患者出现精神不良反应（包括焦虑、躁狂、幻觉、自杀意念）的报道。给有忧郁、躁狂等精神病史者处方Provigil必须特别谨慎。
注意事项

严重肝损害的患者剂量减半，肾功能不全和老年患者服用剂量要酌减，左室肥大、有缺血性心电图改变、胸痛、心律失常或有临床表现的二尖瓣脱垂的患者及近期发生心肌梗塞、不稳定型心绞痛或有精神病史者禁用或慎用。
 
包装规格

片剂：每片含本品，100mg*100 片   200mg* 60 片

新型中枢兴奋药莫达非尼Provigil(Modafinil Tablets)

由于种种原因，处于睡眠剥夺状态下工作的人群不断扩大，不但影响健康，而且也使工作效率和能力降低，因疲倦引发的事故也屡见不鲜。莫达非尼(modaf-inil)是一种新型中枢兴奋剂，它以良好的中枢兴奋作用和较少的毒副作用而受
世人瞩目。
■药理作用机制
莫达非尼能提高正常人群的中枢兴奋性，口服莫达非尼后第1小时到第22小时的脑电图监测表明，反映警觉能力高低的α/θ值升高，偶发的微眠波几乎被完全抑制。对睡眠剥夺人群，睡眠剥夺会造成人的警觉能力和作业能力的下降,服用莫达非尼能有效改善这种状况。研究表明，经过一整夜的睡眠剥夺后，服用200毫克莫达非尼，志愿者的心理运动能力明显高于服用安慰剂组；在长达60小时的睡眠剥夺期间，每隔8小时服用莫达非尼200毫克，仍能较好地维持睡眠剥夺者的中枢处于一定的兴奋状态，使他们保持相当的警觉能力和作业能力。

莫达非尼还具有一定的神经保护作用，用脑损伤动物模型研究发现，莫达非尼能有效地拮抗1-甲基-4-苯基-1，2，3，6-四氢吡啶产生的神经毒作用，使症状得到明显缓解。莫达非尼的神经保护作用还分别在纹状体机械损伤模型和缺血损伤模型中得到证实。莫达非尼中枢兴奋作用与脑中抑制性递质酌-氨基丁酸（GA鄄BA）的减少有关，并受5-羟色胺（5-HT）和去甲肾上腺素的调控。研究中发现，莫达非尼的中枢兴奋作用可能是通过增加谷氨酰胺合成酶，从而减少GABA的生成，并促进神经细胞的解毒功能和能量代谢活动而起作用的。

■药代动力学

莫达非尼口服后迅速完全吸收，大约两小时血浆浓度达到峰值，食物可延缓药物的吸收。莫达非尼在肝脏由细胞色素P450系统的CYP3A4代谢，因此联合应用CYP3A4的诱导剂或抑制剂，会影响莫达非尼的血药浓度及作用周期。莫达非尼经肝脏代谢，生成无治疗作用的两个主要代谢产物莫达非尼酸和莫达非尼砜。药物的清除半衰期为10~15个小时，年轻女性的药物清除率高于年轻男性，老年人的清除率明显低于年轻人。

■临床应用

发作性睡病是一种原因未明的中枢神经系统疾病，其主要症状是白天不能保持清醒或警醒状态，出现无法遏制的睡眠发作和猝倒，患者常因不能自制的睡眠而无法正常生活。莫达非尼作为一种新型催醒药物，能使患者日间摆脱睡意的纠缠，维持正常工作，却不会出现异常兴奋等不良反应，故有“不夜神”之称，是迄今治疗这种睡眠障碍最为理想的药物。研究表明，莫达非尼能有效改善症状，明显减少白天的睡眠时间和次数，而不影响对夜间睡眠的时间和质量。对18名自发性嗜睡症病人和24名发作性嗜睡症病人口服莫达非尼，每日剂量200～500毫克/天，结果显示，自发性嗜睡症和发作性嗜睡症病人的睡眠发作和倦睡明显减少，总有效率分别为83%和71%。莫达非尼还能对抗睡眠剥夺所致的精神运动障碍，改善认知功能，而对夜间睡眠的开始、维持、觉醒及睡眠构成等均无影响，也不影响凌晨的行为和白天的小憩。
莫达非尼还可用于治疗酒精性器质性脑病综合征。有人用莫达非尼治疗酒精性器质性脑病综合征，进行临床心理测验及神经生理学研究，结果表明莫达非尼每日服药后兴奋性增加，临床治疗有效率为85%。
本品的有效剂量为每日200～400毫克，于早、中分两次服用。

■药物相互作用

卡马西平、伊曲康唑、酮康唑等CYP3A4的抑制剂或苯巴比妥、利福平等CYP3A4的诱导剂与莫达非尼同时应用，可能改变莫达非尼的血药浓度。莫达非尼是CYP3A4的诱导剂，它使环孢素的血药浓度降低50%，也可以降低茶碱的血药浓度，并可能降低口服避孕药的疗效。莫达非尼也可增加三环类抗抑郁药、氯丙嗪、地西泮、奥美拉唑、兰索拉唑、苯妥英、普萘洛尔和华法林等药物的血药浓度。
因此，在与上述药物同时应用时，需相应调整剂量，并监测血药浓度。但莫达非尼不会干扰5-HT再摄取抑制剂(SSRl)的代谢。

■不良反应及用药注意事项
本品具有较大的安全性，对血压和心率无影响，无活动增多、耐受性或反弹性思睡等不良反应，也无潜在的成瘾性。主要不良反应有恶心、神经过敏和焦虑，加量过快服药可出现轻至中度头痛。因而，用药宜从小剂量(每日50～100毫克)开始，每4～5天增加50毫克，直至最适剂量(每日200~400毫克)。严重肝损害的患者剂量减半，肾功能不全和老年患者服用剂量要酌减，左室肥大、有缺血性心电图改变、胸痛、心律失常或有临床表现的二尖瓣脱垂的患者及近期发生心肌梗塞、不稳定型心绞痛或有精神病史者禁用或慎用。

PROVIGIL (modafinil)
Modafinil, known chemically as benzhydrylsulphinlacetamide, is a relatively new stimulant-type drug developed by Lafon Laboratories in France. It is sold in the U.S. under the brand name Provigil and internationally under such names as Modiodal, Vigil, Alertec, and Modasomil. Modafinil is specifically characterized as a psychostimulant, and is FDA approved for the treatment of narcolepsy (a disorder characterized by sudden and uncontrollable attacks of deep sleep), mental fatigue, or excessive sleepiness. It is being investigated for a number of other uses, including the treatment of Alzheimer's disease, depression, and attention deficit disorder. Modafinil belongs to a class of drugs known as Eugeroics ("good arousal"), designed to promote a mental state of vigilance and alertness. Modafinil is specifically an alpha 1 adrenoceptor agonist, and exerts its mood and energy  enhancing effects through the increased release of dopamine in the CNS, as well as alterations in local GABA and glutaminate levels.

The use of Modafinil as a stimulant has been shown to be very advantageous over amphetamines. Modafinil is believed to have a much lower potential for abuse (less euphoria), lower peripheral CNS stimulation (less side effects), minimal effects on blood pressure, no interruptions in normal sleeping patterns (no hangover or needing "catch-up" sleep), and an overall greater safety record during clinical trials. This drug is of interest even to the U.S. military, which is looking at it as an energy enhancer for pilots and combat soldiers that need to operate for long periods of time without sleep. This is not as unusual as it may seem at first, as military combat pilots and soldiers have used Dexedrine (an amphetamine) extensively in the past when sleep was difficult. This drug does have its drawbacks, including jitters, jumpiness, poor judgment, and "crashes". However, soldiers on Modafinil report they maintain excellent cognitive functioning for a full 40 hours straight without sleep, with none of the side effects of Dexedrine. Modafinil has been tested in combat situations as recently as Afghanistan and Iraq, and seems poised for official acceptance as a battlefield drug.

Recently, Modafinil has become a popular drug amongst competitive athletes. They use it not simply to stay awake, but as a performance enhancing agent with both stimulant and endurance-increasing properties. This type of use probably comes as a surprise to those who developed this drug, as early reports suggested that this was a "mild" alertness drug, without strong stimulant properties that would improve athletic performance. Apparently, that is not the case. A study conducted just recently in Canada shows a very strong athletic benefit inherent in Modafinil. During this double-blind investigation, a dose of 4 mg per kg of bodyweight (this equates to 200 mg for a 220 lb man) of Modafinil, or placebo, was given to a group of fifteen male volunteers. Three hours after ingestion, aerobic exercise was conducted on a cycle ergometer at 85% V02 max (maximum aerobic power) and time until exhaustion. While taking Modafinil, the men were able to exercise for significantly longer (around 30%), and had greater Oxygen intake at exertion. They also reported lower subjective ratings of perceived exertion (RPE), which suggests that the increased performance was in part due to a significantly less pronounced sensation of fatigue during exercise.

The typical effective dose for both men and women is in the range of 100-400 mg, which is given 2-3 hours prior to athletic competition. As the dosage increases, side effects may start to become an issue, including headache, nausea, nervousness, and anxiety. It is a good idea to start on the low end of the range, and increase by 50-100 mg per application until the optimal level is determined. The areas in which this drug can be applied are vast and essentially include any sport focused on aerobic activity or endurance. It may also work well with those who are forced to repeat short bursts of strength or speed many times during competition, such as shot putting, pole vaulting, or long jumping. Here, it could help the athlete continue performing at optimal levels as the day of competition stretches on. Modafinil is not going to be the most popular drug amongst bodybuilders, as it holds little direct value for building muscle or cutting fat. It may, however, be an effective pre-workout stimulant, helping you spend more time in the gym, and allowing you to attack the weights with more ferocity during the time you spend there.

Although Modafinil has an excellent safety record and profile, it is still considered a drug of potential abuse in the United States. As such, it has been classified as a schedule IV controlled substance, in the same category as Valium and Xanax. This limits its availability somewhat and also places considerable legal penalties on its possession and importation. Therefore, it is probably not a good idea to order this drug freely from international pharmacies on the Internet. Instead, it would be advisable to seek a legitimate domestic prescription for this agent. Since Modafinil has been approved by the FDA for some general uses, including the treatment of metal fatigue this should not be all that difficult. It is quite common for doctors to prescribe this agent to someone who finds him or herself in the middle of a particularly stressful time at work, perhaps suddenly covering a late shift or putting in longer-than usual hours. Such "excuses" would probably afford a modest supply of the drug fairly easily.

Modafinil was very popular amongst competitive athletes for a brief period of time before the IOC became aware of its use and banned it. Some readers may incorrectly be operating under the assumption that this drug is still not being tested for. That is, unfortunately, no longer the case. The use of Modafinil as a performance-enhancing agent was revealed to the public during the designer steroid (BALCO) doping scandal of 2004. It was disclosed that many of the same athletes who tested positive for THG also used the drug. Since then, the IOC has developed a methodology for detecting this chemical, and has implemented it during all standard urine screens. Most of the other international athletic bodies have followed the IOC's lead. Modafinil has since lost all appeal as an "invisible" performance-enhancing drug. Although no longer of great value on the Olympic playing field, in the months and years to come, Modafinil is likely to become popular with bodybuilders and those athletes not subject to drug testing, who may find it an excellent addition to their regular pre-competition pharmaceutical toolbox.