Henchcliffe Claire, Schumacher H Christian, Burgut F Tuna
Weill Medical College of Cornell University, Department of Neurology and Neuroscience, 428 East 72, Street, Suite 400, NY 10021, USA.
Expert Rev Neurother. 2005 Nov;5(6):811-21. doi: 10.1586/14737175.5.6.811.
Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.
单胺氧化酶抑制剂可抑制多巴胺代谢，因此对治疗帕金森病有效。帕金森病与黑质中多巴胺能神经元变性继发的进行性纹状体多巴胺缺乏有关。司来吉兰是目前治疗帕金森病最广泛使用的单胺氧化酶B抑制剂，但生物利用度低且变化不定，且会代谢为L-甲基苯丙胺和L-苯丙胺，存在潜在神经毒性风险。有两种新方法可规避这些潜在缺点。第一，司来吉兰口腔崩解片提供了一种司来吉兰的新型给药形式，通过口腔黏膜快速吸收避免首过代谢，从而使L-甲基苯丙胺和L-苯丙胺的血浆浓度显著降低。司来吉兰口腔崩解片在中度晚期帕金森病患者中证明临床有效且安全。第二，雷沙吉兰是一种新的单胺氧化酶抑制剂，没有已知的神经毒性代谢物。在大型临床试验中，雷沙吉兰在早期帕金森病中作为单一疗法有效，在晚期疾病中作为左旋多巴的辅助疗法也有效。此外，临床数据表明雷沙吉兰具有疾病修饰作用，这可能与帕金森病动物模型中单胺氧化酶B抑制剂的神经保护活性相关。
