Amphetamine, past and present--a pharmacological and clinical perspective.
Amphetamine, past and present--a pharmacological and clinical perspective.
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DOI：
10.1177/0269881113482532
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Nutt DJ
中科院分区：
文献类型：
--
作者：
Heal DJ;Smith SL;Gosden J;Nutt DJ
安非他明是100多年前发现的。从那时起，它已经从一种无需处方即可免费获得的药物转变为一种高度限制的受控药物，其治疗应用仅限于注意力缺陷多动障碍（ADHD）和嗜睡症。本文综述了苯丙胺及其同系物的化学结构与药理作用的关系。安非他明的多种药理作用不仅转化为治疗效果，而且转化为不良事件的产生和娱乐性滥用的可能性。因此，受益/风险平衡是其临床使用的关键挑战。该综述描绘了药物开发的进展，从每天一次的安非他明制剂到lisdexamfetamine，这是第一个被批准用于儿童，青少年和成人ADHD管理的d-安非他明前药。利右苯丙胺传递d-苯丙胺的不寻常的代谢途径对其药理学做出了重要贡献。还讨论了利右苯丙胺独特的药代动力学/药效学特征如何转化为治疗ADHD的持续疗效及其减少娱乐性滥用的可能性。
Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.