Details of the Drug

General Information of Drug (ID: DM93L4X)

• Drug Name: Dexmedetomidine
• Synonyms: Dexmedetomidina; Dexmedetomidinum; MPV 1440; MPV-1440; Precedex (TN); Dexmedetomidine (USAN/INN); (+)-4-((S)-alpha,2,3-Trimethylbenzyl)imidazole; 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole; 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole

Indication

Disease Entry	ICD 11	Status	REF
Irritability	MB24	Approved	[1]
Obstructive sleep apnea	7A41	Approved	[2]
Traumatic brain injury	NA07.Z	Approved	[2]
Respiratory failure	CB41	Investigative	[2]

• Therapeutic Class: Hypnotics and Sedatives
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 200.28
  Logarithm of the Partition Coefficient (xlogp); 3.1
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 11 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [3]
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.089 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.06% [3]
  Vd: The volume of distribution (Vd) of drug is 118 L []
• Chemical Identifiers:
  Formula: C13H16N2
  IUPAC Name: 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole
  Canonical SMILES: CC1=C(C(=CC=C1)[C@H](C)C2=CN=CN2)C
  InChI: InChI=1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)/t11-/m0/s1
  InChIKey: CUHVIMMYOGQXCV-NSHDSACASA-N
• Cross-matching ID:
  PubChem CID: 5311068
  ChEBI ID: CHEBI:4466
  CAS Number: 113775-47-6
  DrugBank ID: DB00633
  TTD ID: D0U3DU
  INTEDE ID: DR0472
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[6]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[8]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dexmedetomidine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Olopatadine	DMKMWQG	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Olopatadine.	Conjunctiva disorder [9A60]	[9]
Propofol	DMB4OLE	Moderate	Additive cardiorespiratory depression effects by the combination of Dexmedetomidine and Propofol.	Corneal disease [9A76-9A78]	[10]
Ethanol	DMDRQZU	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Ethanol.	Cystitis [GC00]	[9]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Esketamine.	Depression [6A70-6A7Z]	[11]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[12]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Lasmiditan.	Migraine [8A80]	[13]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Flibanserin.	Mood disorder [6A60-6E23]	[14]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Thalidomide.	Multiple myeloma [2A83]	[15]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Dexmedetomidine and Apraclonidine.	Optic nerve disorder [9C40]	[16]
Dextropropoxyphene	DM23HCX	Major	Additive CNS depression effects by the combination of Dexmedetomidine and Dextropropoxyphene.	Pain [MG30-MG3Z]	[17]
Buprenorphine	DMPRI8G	Major	Additive CNS depression effects by the combination of Dexmedetomidine and Buprenorphine.	Pain [MG30-MG3Z]	[18]

References

• [1] 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. (Ligand id: 521).
• [2] Dexmedetomidine FDA Label
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
• [6] Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes. Biomed Chromatogr. 2010 Aug;24(8):868-77.
• [7] Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication. Expert Rev Clin Pharmacol. 2018 Sep;11(9):917-922.
• [8] Predominant role of peripheral catecholamines in the stress-induced modulation of CYP1A2 inducibility by benzo(alpha)pyrene. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):35-44.
• [9] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
• [10] Gill SS, Wright EM, Reilly CS "Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study." Br J Anaesth 65 (1990): 760-5. [PMID: 2265045]
• [11] Cerner Multum, Inc. "Australian Product Information.".
• [12] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [13] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
• [14] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
• [15] Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
• [16] Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
• [17] Hansen BS, Dam M, Brandt J, et al "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67. [PMID: 6998251]
• [18] Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8. [PMID: 3592200]