Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM8ZG2I)

• Drug Name: O-DESMETHYL TRAMADOL Drug Info
• Synonyms: O-Desmethyltramadol; O-DESMETHYL TRAMADOL; CHEMBL1400; (-)-O-Desmethyl Tramadol; 80456-81-1; 2-[(Dimethylamino)methyl]-1-(3-hydroxyphenyl)cyclohexanol; CHEMBL201556; O-Demethyl tramadol; tramadol M1 metabolite; Mono-O-demethyltramadol; 144830-15-9; 3-{(1R,2R)-2-[(dimethylamino)methyl]-1-hydroxycyclohexyl}phenol; 3-((1R,2R)-2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenol; (+)-O-Desmethyltramadol; SCHEMBL2517055; CTK8E8372; UWJUQVWARXYRCG-HIFRSBDPSA-N; ZINC2509756; BDBM50176258; BDBM50176263; Phenol, 3-(2-((dimethylamino)me

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9838803
  ChEBI ID: CHEBI:165221
  CAS Number: CAS 144830-14-8
  TTD Drug ID: DM8ZG2I

Molecule-Related Drug Atlas

Drug(s) Targeting Serotonin transporter (SERT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[4]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[5]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[6]
Vortioxetine	DM6F1PU	Major depressive disorder	6A70.3	Approved	[7]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[8]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[9]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[10]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[6]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[6]
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[6]

Drug(s) Targeting Opioid receptor mu (MOP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[11]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[12]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[13]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[14]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[15]
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[16]
Naloxegol	DML0B41	Opioid-induced constipation	DB32.1	Approved	[17]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[18]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[19]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[20]

Drug(s) Targeting Opioid receptor delta (OPRD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Codeine	DMJX6ZG	Allergic rhinitis	CA08.0	Approved	[21]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[22]
Loperamide	DMOJZQ9	Diarrhea	ME05.1	Approved	[23]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[18]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[24]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[21]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[25]
Met-enkephalin	DMSZFTP	Pain	MG30-MG3Z	Phase 2	[26]
AZD-2327	DM8FZOG	Anxiety disorder	6B00-6B0Z	Phase 2	[27]
ADL-5747	DMMUPTN	Pain	MG30-MG3Z	Phase 2	[28]

Drug(s) Targeting Opioid receptor kappa (OPRK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nalbuphine	DMOSQGU	Pain	MG30-MG3Z	Approved	[6]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[19]
CHLOROXINE	DMFZBMQ	Erythema	ME64.0	Approved	[29]
Difelikefalin	DMHZBEO	Pruritus	EC90	Approved	[30]
Dezocine	DMJDB0Y	Pain	MG30-MG3Z	Approved	[31]
Asimadoline	DMND3AB	Diarrhea-predominant irritable bowel syndrome	DD91.01	Phase 3	[32]
JNJ 67953964	DMJ8Y5N	Major depressive disorder	6A70.3	Phase 3	[33]
PHN-131	DM1SV8I	Pain	MG30-MG3Z	Phase 2/3	[34]
CR-845	DMJYTUQ	Pain	MG30-MG3Z	Phase 2/3	[35]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[25]

Drug(s) Affected By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[36]
Paliperidone	DM7NPJS	Psychotic disorder	6A20-6A25	Approved	[37]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[38]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[39]
Oxatomide	DM1F42Z	Hay fever	CA08.00	Approved	[40]
Cinacalcet	DMCX0K3	Hyperparathyroidism	5A51	Approved	[41]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[42]
Pentamidine	DMHZJCG	African trypanosomiasis	1F51	Approved	[43]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[44]
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[45]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Inhibitor	[1]
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Inhibitor	[1]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[1]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Biotransformations	[3]

References

• [1] Syntheses and opioid receptor binding properties of carboxamido-substituted opioids. Bioorg Med Chem Lett. 2009 Jan 1;19(1):203-8.
• [2] Derivatives of tramadol for increased duration of effect. Bioorg Med Chem Lett. 2006 Feb;16(3):691-4.
• [3] Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol. 2008 Feb;28(1):78-83. doi: 10.1097/JCP.0b013e318160f827.
• [4] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [5] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [8] Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
• [9] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [10] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [11] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [12] Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
• [13] Clinical pipeline report, company report or official report of signaturerx.
• [14] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [15] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [16] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [17] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [18] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [19] Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
• [20] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 319).
• [21] Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16.
• [22] Identification of opioid ligands possessing mixed micro agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone [correction of hydropmorphone]. J Med Chem. 2004 Mar 11;47(6):1400-12.
• [23] Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8.
• [24] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [25] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [26] Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon. Eur J Pharmacol. 1994 Sep 1;262(1-2):33-9.
• [27] Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther. 2011 Jul;338(1):195-204.
• [28] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 317).
• [29] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [30] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [31] Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
• [32] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [33] Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders. Handb Exp Pharmacol. 2022;271:473-491.
• [34] Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
• [35] Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.
• [36] Human recombinant cytochrome P450 enzymes display distinct hydrogen peroxide generating activities during substrate independent NADPH oxidase reactions. Toxicol Sci. 2014 Oct;141(2):344-52. doi: 10.1093/toxsci/kfu133. Epub 2014 Jul 24.
• [37] Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl). 1999 Dec;147(3):300-5. doi: 10.1007/s002130051171.
• [38] Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450. J Toxicol Sci. 2016 Feb;41(1):143-6.
• [39] Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011 Nov;39(11):2049-56. doi: 10.1124/dmd.111.041384. Epub 2011 Aug 5.
• [40] Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34.
• [41] Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.
• [42] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [43] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [44] Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin Pharmacol Ther. 2001 Oct;70(4):327-35.
• [45] Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos. 2003 Jun;31(6):768-72.