Finberg J P M, Gross A, Bar-Am O, Friedman R, Loboda Y, Youdim M B H
Department of Pharmacology, Rappaport Family Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
Br J Pharmacol. 2006 Nov;149(6):647-56. doi: 10.1038/sj.bjp.0706908. Epub 2006 Oct 3.
Postural hypotension is a common side-effect of L-DOPA treatment of Parkinson's disease, and may be potentiated when L-DOPA is combined with selegiline, a selective inhibitor of monoamine oxidase B (MAO-B). Rasagiline is a new, potent and selective MAO-B inhibitor, which does not possess the sympathomimetic effects of selegiline. We have studied the effects of these selective MAO inhibitors, L-DOPA and dopamine on the cardiovascular system of the rat.
Blood pressure and heart rate was measured in conscious rats following acute or chronic administration of rasagiline, selegiline and L-DOPA, by comparison with the selective MAO-A inhibitor clorgyline, or the MAO-A/B inhibitor tranylcypromine. Cardiovascular responses, catecholamine release, and modification of pressor response to dopamine were studied in pithed rats.
In conscious rats neither rasagiline nor selegiline caused significant potentiation of the effects of L-DOPA (50, 100, 150 mg.kg(-1)) on blood pressure or heart rate at doses which selectively inhibited MAO-B, but L-DOPA responses were potentiated by clorgyline and tranylcypromine. In rats treated twice daily for 8 days with L-DOPA and carbidopa, selegiline (5 mg.kg(-1)) but not rasagiline (0.2 mg.kg(-1)) caused a significant hypotensive response to L-DOPA and carbidopa, although both drugs caused similar inhibition of MAO-A and MAO-B. In pithed rats, selegiline but not rasagiline increased catecholamine release and heart rate, and potentiated dopamine pressor response at MAO-B selective dose.
The different responses to the two MAO-B inhibitors may be explained by the amine releasing effect of amphetamine metabolites formed from selegiline.
体位性低血压是帕金森病左旋多巴治疗的常见副作用，当左旋多巴与单胺氧化酶B（MAO-B）的选择性抑制剂司来吉兰联用时，该副作用可能会增强。雷沙吉兰是一种新型、强效且选择性的MAO-B抑制剂，不具有司来吉兰的拟交感神经作用。我们研究了这些选择性MAO抑制剂、左旋多巴和多巴胺对大鼠心血管系统的影响。
通过与选择性MAO-A抑制剂氯吉兰或MAO-A/B抑制剂反苯环丙胺比较，在清醒大鼠急性或慢性给予雷沙吉兰、司来吉兰和左旋多巴后测量血压和心率。在脊髓横断大鼠中研究心血管反应、儿茶酚胺释放以及对多巴胺升压反应的改变。
在清醒大鼠中，雷沙吉兰和司来吉兰在选择性抑制MAO-B的剂量下，均未引起左旋多巴（50、100、150mg·kg⁻¹）对血压或心率影响的显著增强，但氯吉兰和反苯环丙胺增强了左旋多巴的反应。在用左旋多巴和卡比多巴每日两次治疗8天的大鼠中，司来吉兰（5mg·kg⁻¹）而非雷沙吉兰（-1）引起了对左旋多巴和卡比多巴的显著降压反应，尽管两种药物对MAO-A和MAO-B的抑制作用相似。在脊髓横断大鼠中，司来吉兰而非雷沙吉兰在MAO-B选择性剂量下增加了儿茶酚胺释放和心率，并增强了多巴胺升压反应。
对两种MAO-B抑制剂的不同反应可能由司来吉兰形成的苯丙胺代谢产物的胺释放作用来解释。
