Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIY42ARH1)
  Drug Name Oxcarbazepine Drug Info Methylene blue Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticonvulsants Antidotes/Mao Inhibitors
  Structure

 Mechanism of Oxcarbazepine-Methylene blue Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Oxcarbazepine 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 Oxcarbazepine and Methylene blue 

Recommended Action
      Management In general, dibenzazepine derivatives should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with tricyclic antidepressants, and vice versa.

References
1 Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
2 Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5. [PMID: 9861909]
3 Dardennes RM, Even C, Ballon N, Bange F "Serotonin syndrome caused by a clomipramine-moclobemide interaction." J Clin Psychiatry 59 (1998): 382-3. [PMID: 9714270]
4 de la Fuente JR, Berlanga C, Leon-Andrade C "Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports." J Clin Psychiatry 47 (1986): 40-1. [PMID: 3941059]
5 De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
6 Feighner JP, Herbstein J, Damlouji N "Combined MAOI, TCA, and direct stimulant therapy of treatment- resistant depression." J Clin Psychiatry 46 (1985): 206-9. [PMID: 3997787]
7 Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2. [PMID: 8748434]
8 Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62. [PMID: 14197995]
9 Graham PM, Potter JM, Paterson J "Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction." Lancet 2 (1982): 440. [PMID: 6124828]
10 Hardman JG, Gilman AG, Limbird LE eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 9th ed." New York, NY: McGraw-Hill (1995):.
11 Joffe RT, Post RM, Uhde TW "Lack of pharmacokinetic interaction of carbamazepine with tranylcypromine." Arch Gen Psychiatry 42 (1985): 738. [PMID: 4015316]
12 Kay DW, Garside RF, Fahy TJ "A double-blind trial of phenelzine and amitriptyline in depressed out- patients. A possible differential effect of the drugs on symptoms." Br J Psychiatry 123 (1973): 63-7. [PMID: 4580991]
13 Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8. [PMID: 17122225]
14 Ketter TA, Post RM, Parekh PI, Worthington K "Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression." J Clin Psychiatry 56 (1995): 471-5. [PMID: 7559374]
15 Kline SS, Mauro LS, Scala-Bennett DM, Zick D "Serotonin syndrome versus neuroleptic malignant death syndrome as a cause of death." Clin Pharm 8 (1989): 510-4. [PMID: 2568897]
16 Lader M "Combined use of tricyclic antidepressants and monoamine oxidase inhibitors." J Clin Psychiatry 44 (1983): 20-4. [PMID: 6355073]
17 Lefebvre H, Noblet C, Morre N, Wolf LM "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf) 42 (1995): 95-8. [PMID: 7889639]
18 Lydiard RB, White D, Harvey B, Taylor A "Lack of pharmacokinetic interaction between tranylcypromine and carbamazepine." J Clin Psychopharmacol 7 (1987): 360. [PMID: 3680612]
19 Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6. [PMID: 8909274]
20 Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763. [PMID: 9330840]
21 Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8. [PMID: 8257462]
22 Otte W, Birkenhager TK, van den Broek WW "Fatal interaction between tranylcypromine and imipramine." Eur Psychiatry 18 (2003): 264-5. [PMID: 12927331]
23 Pascual J, Combarros O, Berciano J "Partial status epilepticus following single low dose of chlorimipramine in a patient on MAO-inhibitor treatment." Clin Neuropharmacol 10 (1987): 565-7. [PMID: 3427564]
24 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
25 Product Information. Azilect (rasagiline). Teva Pharmaceuticals USA, North Wales, PA.
26 Product Information. Eldepryl (selegiline). Somerset Pharmaceuticals Inc, Tampa, FL.
27 Product Information. Emsam (selegiline). Bristol-Myers Squibb, Princeton, NJ.
28 Product Information. Flexeril (cyclobenzaprine). Merck & Co, Inc, West Point, PA.
29 Product Information. Furoxone (furazolidone). Roberts Pharmaceutical Corporation, Eatontown, NJ.
30 Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
31 Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
32 Product Information. Methylene Blue (methylene blue). American Regent Laboratories Inc, Shirley, NY.
33 Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
34 Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
35 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]
36 Spiker DG, Pugh DD "Combining tricyclic and monoamine oxidase inhibitor antidepressants." Arch Gen Psychiatry 33 (1976): 828-30. [PMID: 942286]
37 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]
38 Tackley RM, Tregaskis B "Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction." Anaesthesia 42 (1987): 760-3. [PMID: 3631476]
39 Waghray SN, Francis K "Epilepsy as an adverse reaction to combined therapy of MAOIs and tricyclics." J R Soc Med 77 (1984): 346. [PMID: 6425500]
40 White K, Pistole T, Boyd JL "Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study." Am J Psychiatry 137 (1980): 1422-5. [PMID: 7435677]
41 White K, Simpson G "Combined MAOI-tricyclic antidepressant treatment: a reevaluation." J Clin Psychopharmacol 1 (1981): 264-82. [PMID: 7037873]
42 Wright SP "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet 1 (1978): 284-5. [PMID: 74715]
43 Yatham LN, Barry S, Mobayed M, Dinan TG "Is the carbamazepine-phenelzine combination safe?." Am J Psychiatry 147 (1990): 367. [PMID: 2309956]
44 Zetin M "Combined use of trimipramine and phenelzine in depression." J Nerv Ment Dis 170 (1982): 246-7. [PMID: 7062012]