Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIXOQ6WF1)
Drug Name			Maprotiline		Drug Info		Methylene blue		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antidepressants				Antidotes/Mao Inhibitors
Structure

Mechanism of Maprotiline-Methylene blue Interaction (Severity Level: Major)
Additive serotonergic effects Click to Show/Hide Mechanism Graph

Drug Name		Maprotiline				Methylene blue
Mechanism		Serotonergic effects Serotonin transporter Inhibitor				Serotonergic effects Monoamine oxidase non-selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Serotonin transporter				× Structure Sequence METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
		Gene Name		SLC6A4
		Uniprot ID		SC6A4_HUMAN
		KEGG Pathway		hsa:6532
		Protein Family		Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
		Protein Function		Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. 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 serotonergic effects by the combination of Maprotiline and Methylene blue

Recommended Action
Management		Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life.

References
1	Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Gillman PK "Methylene blue and serotonin toxicity: definite causal link." Psychosomatics 51 (2010): 448-9. [PMID: 20833947]
4	Gillman PK "Methylene blue is a potent monoamine oxidase inhibitor." Can J Anaesth 55 (2008): 311-2 author reply 312. [PMID: 18451123]
5	Heritier Barras AC, Walder B, Seeck M "Serotonin syndrome following Methylene Blue infusion: a rare complication of antidepressant therapy." J Neurol Neurosurg Psychiatry 81 (2010): 1412-3. [PMID: 20547626]
6	Khavandi A, Whitaker J, Gonna H "Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue." Med J Aust 189 (2008): 534-5. [PMID: 18976207]
7	Ng BK, Cameron AJ "The role of methylene blue in serotonin syndrome: a systematic review." Psychosomatics 51 (2010): 194-200. [PMID: 20484716]
8	Ng BK, Cameron AJ, Liang R, Rahman H. Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review.?Can J Anaesth. 2008;55(1):36-41. [PMID: 18166746]
9	FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when linezolid (Ayvox) is given to patients taking certain psychiatric medications.".
10	FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications.".