Details of the Drug

General Information of Drug (ID: DMT5HA4)

Drug Name

Ketamine

Synonyms

Calypsol; Cetamina; Green; Ketaject; Ketalar; Ketaminum; Ketanest; Ketoject; Ketolar; Tekam; KETAMINE HCL; Ketalar base; Ketamine Base; Special K; Special K [street name]; CLSTA 20; T385; Cetamina [INN-Spanish]; Dl-Ketamine; Ketalar (TN); Ketamine (INN); Ketamine [INN:BAN]; Ketaminum [INN-Latin]; Ketanest (TN); Ketaset (TN); Tekam (TN); Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-(9CI); Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-, (+-)-(9CI); Cyclohexanone, 2-(o-chlorophenyl)-2-(methylamino)-, (+/-)-(8CI); (+/-)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone; (+/-)-2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone; 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone; 2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one; 2-(Methylamino)-2-(2-chlorophenyl)cyclohexanone; 2-(o-Chlorophenyl)-2-(methylamino)-cyclohexanone; 2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]
Anxiety	N.A.	Approved	[2]
Bipolar disorder	6A60	Approved	[2]
Depression	6A70-6A7Z	Approved	[2]
Traumatic brain injury	NA07.Z	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]
Chronic pain	MG30	Investigative	[2]
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Therapeutic Class

Analgesics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

237.72

Logarithm of the Partition Coefficient (xlogp)

2.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.75 mg/L [4]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
Bioavailability: The bioavailability of drug is 93% [4]
Clearance: The clearance of drug is 1.36 L/h/kg [6]
Elimination: Pharmacokinetic studies have resulted in the recovery of 85-95% of the administered dose in urine mainly in the form of metabolites [7]
Half-life: The concentration or amount of drug in body reduced by one-half in 186 minutes [4]
Metabolism: The drug is metabolized via the hepatic [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8.41285 micromolar/kg/day [8]
Unbound Fraction: The unbound fraction of drug in plasma is 0.47% [9]
Vd: The volume of distribution (Vd) of drug is 0.3713 L/kg [10]
Water Solubility: The ability of drug to dissolve in water is measured as 200 mg/mL [5]

Chemical Identifiers

Formula: C13H16ClNO
IUPAC Name: 2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one
Canonical SMILES: CNC1(CCCCC1=O)C2=CC=CC=C2Cl
InChI: InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3
InChIKey: YQEZLKZALYSWHR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3821
ChEBI ID: CHEBI:6121
CAS Number: 6740-88-1
DrugBank ID: DB01221
TTD ID: D0UM7O
VARIDT ID: DR00685
INTEDE ID: DR0903

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Antagonist	[11]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[12]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[12]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[13]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Gene/Protein Processing	[14]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Gene/Protein Processing	[15]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Drug Response	[16]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Protein Interaction/Cellular Processes	[17]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[18]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Gene/Protein Processing	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[17]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Gene/Protein Processing	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[17]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Ketamine caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[19]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Ketamine caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[20]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Ketamine caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[21]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Ketamine caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[22]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Ketamine and Esketamine.	Depression [6A70-6A7Z]	[23]
Cenobamate	DM8KLU9	Moderate	Increased metabolism of Ketamine caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[24]
Darunavir	DMN3GCH	Moderate	Decreased metabolism of Ketamine caused by Darunavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[25]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Ketamine caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[26]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Ketamine caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[21]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Ketamine caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[27]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Ketamine caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[28]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Ketamine caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[21]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Ketamine and Flibanserin.	Mood disorder [6A60-6E23]	[29]
Levomethadyl Acetate	DM06HG5	Major	Additive CNS depression effects by the combination of Ketamine and Levomethadyl Acetate.	Opioid use disorder [6C43]	[29]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Ketamine caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[23]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Ketamine caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[30]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Ketamine caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[31]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Ketamine caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[32]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Ketamine caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[33]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Ketamine caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[21]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Ketamine caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[23]
LEE011	DMMX75K	Moderate	Decreased metabolism of Ketamine caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[34]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Ketamine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[35]
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References

1	FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 076092.
2	Ketamine FDA Label
3	ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
4	Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982 May;71(5):539-42.
5	BDDCS applied to over 900 drugs
6	Fanta S, Kinnunen M, Backman JT, Kalso E: Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. Eur J Clin Pharmacol. 2015 Apr;71(4):441-7. doi: 10.1007/s00228-015-1826-y. Epub 2015 Mar 1.
7	Ketamine monograph
8	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
9	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
10	Pypendop BH, Ilkiw JE: Pharmacokinetics of ketamine and its metabolite, norketamine, after intravenous administration of a bolus of ketamine to isoflurane-anesthetized dogs. Am J Vet Res. 2005 Dec;66(12):2034-8. doi: 10.2460/ajvr.2005.66.2034.
11	Ketamine modulates theta and gamma oscillations. J Cogn Neurosci. 2010 Jul;22(7):1452-64.
12	Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos. 2002 Jul;30(7):853-8.
13	Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-1. Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F961-F972. doi: 10.1152/ajprenal.00686.2016. Epub 2017 Mar 22.
14	Ketamine promotes the amyloidogenic pathway by regulating endosomal pH. Toxicology. 2022 Apr 15;471:153163. doi: 10.1016/j.tox.2022.153163. Epub 2022 Apr 1.
15	Ketamine hypertension and the renin-angiotensin system. Clin Exp Hypertens A. 1983;5(6):875-83. doi: 10.3109/10641968309081814.
16	The apolipoprotein E epsilon 4 allele is associated with blunting of ketamine-induced psychosis in schizophrenia. A preliminary report. Neuropsychopharmacology. 1998 Nov;19(5):445-8. doi: 10.1016/S0893-133X(98)00031-1.
17	Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway. Br J Anaesth. 2009 Jan;102(1):80-9. doi: 10.1093/bja/aen322. Epub 2008 Nov 9.
18	Lipoxin A4 methyl ester attenuated ketamine-induced neurotoxicity in SH-SY5Y cells via regulating leptin pathway. Toxicol In Vitro. 2023 Jun;89:105581. doi: 10.1016/j.tiv.2023.105581. Epub 2023 Mar 11.
19	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
20	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
21	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
22	Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
23	Cerner Multum, Inc. "Australian Product Information.".
24	Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
25	Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
26	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
27	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
28	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
29	Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
30	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
31	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
32	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
33	Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
34	DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
35	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.