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Pathway Description
Selegiline Action Pathway
Homo sapiens
Drug Action Pathway
Selegiline is an irreversible monoamine oxidase inhibitor (MAOIs). It is indicated for the initial treatment of Parkinson's disease and for adjunct therapy in patients that are having decreased response to levodopa or carbadopa. This molecule can also be used as a palliative treatment of Alzheimer's disease and at very high doses, for the treatment of depression. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO-A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. MAO-B is involved in the nigrostriatal pathways, it accelerates the breakdown of dopamine in the cells. Selegiline binds selectively to MAO-B, this hinders the microsomal breakdown of dopamine, thereby amplifying the dopaminergic activities in the substantial nigra. At higher doses, selegiline can also binds MAO-A, enabling its application in depression treatment. This drug is administered as an oral tablet.
References
Selegiline Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Magyar K, Tothfalusi L: Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm. 1984 Jul-Aug;36(4):373-84.
Pubmed: 6441926
Engberg G, Elebring T, Nissbrandt H: Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J Pharmacol Exp Ther. 1991 Nov;259(2):841-7.
Pubmed: 1658311
Macleod AD, Counsell CE, Ives N, Stowe R: Monoamine oxidase B inhibitors for early Parkinson's disease. Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD004898. doi: 10.1002/14651858.CD004898.pub2.
Pubmed: 16034956
Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet. 2002;41(4):261-309. doi: 10.2165/00003088-200241040-00003.
Pubmed: 11978145
Culpepper L, Kovalick LJ: A review of the literature on the selegiline transdermal system: an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression. Prim Care Companion J Clin Psychiatry. 2008;10(1):25-30. doi: 10.4088/pcc.v10n0105.
Pubmed: 18311418
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