Details of Drug Interaction | MecDDI

Drug General Information (ID: DDID50FVX2)
Drug Name			Sildenafil		Drug Info		Selegiline		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Impotence Agents/Agents For Pulmonary Hypertension				Dopaminergic Antiparkinsonism Agents/Mao Inhibitors
Structure

Mechanism of Sildenafil-Selegiline Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Sildenafil				Selegiline
Mechanism		Hypotensive effects Phosphodiesterase 5A Inhibitor				Hypotensive effects Monoamine oxidase non-selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Phosphodiesterase 5A				× Structure Sequence MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
		Gene Name		PDE5A
		Uniprot ID		PDE5A_HUMAN
		KEGG Pathway		hsa:8654
		Protein Family		Cyclic nucleotide phosphodiesterase family
		Protein Function		Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334). Click to Show/Hide
Key Mechanism Factor 2
		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
Mechanism Description		Additive hypotensive effects by the combination of Sildenafil and Selegiline

Recommended Action
Management		Caution is advised during coadministration of MAOIs and other medications with hypotensive effects, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Ambulatory patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
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7	Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
8	Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
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10	Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
11	Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
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13	Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]