Rasagiline Monoamine oxidase inhibitors

Chen, J.J., Swope, D.M., and Dashtipour, K. 2007. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatanent of Parkinson s disease. Clin Ther, 2S (9) 1825-49. 

Monoamine Oxidases and their Inhibitors. Figure 2 Structures of MAO inhibitors. In the top row, the structural similarity between selegiline/L-deprenyl and methamphetamine is shown. Below are the aminoindan series of propargylamine compounds such as rasagiline. Next, the bifunctional MAO and cholinesterase inhibitors (ladostigil) and lastly, the iron chelator-MAO inhibitors. 

Rasagiline, another monoamine oxidase B inhibitor, is more potent than selegiline in preventing MPTP-induced parkinsonism and is currently under study as a neuroprotective agent. 

Monoamine-oxidase B inhibitors, such as selegiline and rasagiline, have a use alone in the management of early disease. Early treatment with selegiline alone has been shown to delay the need for levodopa therapy for some months, but other more effective drugs are preferred. Both dmgs can be used in conjunction with levodopa preparations to reduce end-of-dose deterioration in advanced disease. 

Monoamine oxidase type B inhibitors (rasagiline, selegiline) reduce the metabolism of dopamine by MAO-B. They are useful to delay disease progression in the early stages of the disease and as an adjunct to levodopa. 

FIGURE 20-7 Pharmacological preservation of L-DOPA and striatal dopamine. The principal site of action of inhibitors of catechol-O-methyltransferase (COMT) (such as tolcapone and entacapone) is in the peripheral circulation. They block the O-methylation of levodopa (l-DOPA) and increase the fraction of the drug available for delivery to the brain. Tolcapone also has effects in the CNS. Inhibitors of MAO-B, such as low-dose selegiline and rasagiline, will act within the CNS to reduce oxidative deamination of DA, thereby enhancing vesicular stores. AAD, aromatic L-amino acid decarboxylase DA, dopamine DOPAC, 3,4-dihydroxyphenylacetic acid MAO, monoamine oxidase 3MT, 3-methoxyl-tyramine 3-O-MD, 3-O-methyl DOPA. 

Weinreb, O., Amit, T., Bar-Am, O., Youdim, M.B.H. 2010. Rasagiline a novel anti-Par-kinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol, 92(3) 330-344. 

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