Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIYKH7LGX)
Drug Name			Procarbazine		Drug Info		Safinamide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Dopaminergic Antiparkinsonism Agents
Structure

Mechanism of Procarbazine-Safinamide Interaction (Severity Level: Major)
Additive serotonergic effects Click to Show/Hide Mechanism Graph

Drug Name		Procarbazine				Safinamide
Mechanism		Serotonergic effects Monoamine oxidase non-selective Inhibitor				Serotonergic effects Monoamine oxidase-B selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Monoamine oxidase				Structure Sequence
		Protein Family		Flavin monoamine oxidase family
		Protein Function		Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Monoamine oxidase type B				× Structure Sequence MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYVGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRTMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVSALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQTRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYYKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERLKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRIYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTFLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
		Gene Name		MAOB
		Uniprot ID		AOFB_HUMAN
		KEGG Pathway		hsa:4129
		Protein Family		Flavin monoamine oxidase family
		Protein Function		Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Preferentially degrades benzylamine and phenylethylamine (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Click to Show/Hide
Mechanism Description		Additive serotonergic effects by the combination of Procarbazine and Safinamide

Recommended Action
Management		Concurrent use of selective MAO-B inhibitors with other MAO inhibitors is considered contraindicated. At least 14 days should elapse between discontinuation of a nonselective MAO inhibitor and initiation of treatment with a selective MAO inhibitor, and vice versa. The recommended dosages of selective MAO-B inhibitors should not be exceeded, as it can increase the risk of nonselective MAO inhibition and precipitation of a hypertensive crisis.

References
1	Product Information. Azilect (rasagiline). Teva Pharmaceuticals USA, North Wales, PA.
2	Product Information. Eldepryl (selegiline). Somerset Pharmaceuticals Inc, Tampa, FL.
3	Product Information. Emsam (selegiline). Bristol-Myers Squibb, Princeton, NJ.