Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIGFBZVAH)
  Drug Name Trandolapril Drug Info Isocarboxazid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Antidepressants
  Structure

 Mechanism of Trandolapril-Isocarboxazid Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trandolapril Isocarboxazid
      Mechanism Antihypertensive agent
Angiotensin-converting enzyme  Inhibitor 		Hypotensive effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name Angiotensin-converting enzyme
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Structure Sequence
MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRIIGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDPDLTNILASSRSYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRSWYNSPTFEDDLEHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQSWENIYDMVVPFPDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSMLEKPADGREVVCHASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPVSLRRGANPGFHEAIGDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFLPFGYLVDQWRWGVFSGRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNVTPYIRYFVSFVLQFQFHEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQEVLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGIDLVTDEAEASKFVEEYDRTSQVVWNEYAEANWNYNTNITTETSKILLQKNMQIANHTLKYGTQARKFDVNQLQNTTIKRIIKKVQDLERAALPAQELEEYNKILLDMETTYSVATVCHPNGSCLQLEPDLTNVMATSRKYEDLLWAWEGWRDKAGRAILQFYPKYVELINQAARLNGYVDAGDSWRSMYETPSLEQDLERLFQELQPLYLNLHAYVRRALHRHYGAQHINLEGPIPAHLLGNMWAQTWSNIYDLVVPFPSAPSMDTTEAMLKQGWTPRRMFKEADDFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHASAWDFYNGKDFRIKQCTTVNLEDLVVAHHEMGHIQYFMQYKDLPVALREGANPGFHEAIGDVLALSVSTPKHLHSLNLLSSEGGSDEHDINFLMKMALDKIAFIPFSYLVDQWRWRVFDGSITKENYNQEWWSLRLKYQGLCPPVPRTQGDFDPGAKFHIPSSVPYIRYFVSFIIQFQFHEALCQAAGHTGPLHKCDIYQSKEAGQRLATAMKLGFSRPWPEAMQLITGQPNMSASAMLSYFKPLLDWLRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGLDLDAQQARVGQWLLLFLGIALLVATLGLSQRLFSIRHRSLHRHSHGPQFGSEVELRHS
Gene Name ACE
Uniprot ID ACE_HUMAN
KEGG Pathway hsa:1636
Protein Family Peptidase M2 family
Protein Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.
    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 Trandolapril and Isocarboxazid 

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
1 Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
2 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]
3 Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62. [PMID: 14197995]
4 Golwyn DH, Sevlie CP "Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension." J Clin Psychopharmacol 13 (1993): 77-8. [PMID: 8486823]
5 Kronig MH, Roose SP, Walsh BT, Woodring S, Glassman AH "Blood pressure effects of phenelzine." J Clin Psychopharmacol 3 (1983): 307-10. [PMID: 6630590]
6 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
7 Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
8 Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
9 Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
10 Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
11 Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
12 Reggev A, Vollhardt BR "Bradycardia induced by an interaction between phenelzine and beta blockers." Psychosomatics 30 (1992): 106-8. [PMID: 2913594]
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]