Details of the Drug

General Information of Drug (ID: DM3FXMA)

Drug Name

Naloxone

Synonyms

Nalone; Nalossone; Naloxona; Naloxonum; Narcan; Narcanti; Narcon; DBL Naloxone; Nalossone [DCIT]; Naloxone HCl; EN 1530base; DBL Naloxone (TN); L-Naloxone; N-Allylnoroxymorphone; Nalone (TN); Naloxona [INN-Spanish]; Naloxone (INN); Naloxone [INN:BAN]; Naloxonum [INN-Latin]; Narcan (TN); Narcanti (TN); N-Allyl-noroxymorphone; L-N-Allyl-14-hydroxynordihydromorphinone; L-N-Allyl-7,8-dihydro-14-hydroxynormorphinone; N-Allyl-4,5alpha-epoxy-3,14-dihydroxy-6-morphinanon; Morphinan-6-one, 17-allyl-4,5alpha-epoxy-3,14-dihydroxy-(8CI); Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5alpha)-(9CI); (-)-N-allyl-14-hydroxynordihydroxymorphinan-6-one; (-)-Naloxone; (5alpha)-3,14-dihydroxy-17-prop-2-en-1-yl-4,5-epoxymorphinan-6-one; (5alpha)-4,5-Epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one; 1-N-Allyl-14-hydroxynordihydromorphinone; 1-N-Allyl-7,8-dihydro-14-hydroxynormorphinone; 12-Allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-4aH-8,9c-iminoethanophenanthro(4,5-bcd)furanone; 12-Allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-4aH-8,9c-iminoethanophenanthro[4,5-bcd]furan-5(6H)-one; 17-Allyl-4,5-alpha-epoxy-3,14-dihydroxymorphinan-6-one; 17-Allyl-4,5alpha-epoxy-3,14-dihydroxymorphinan-6-one; 17-allyl-3,14-dihydroxy-4,5alpha-epoxymorphinan-6-one; 3,14-dihydroxy-17-(prop-2-en-1-yl)-4,5alpha-epoxymorphinan-6-one

Indication

Disease Entry	ICD 11	Status	REF
Narcotic depression	6A7Z	Approved	[1]
Pain	MG30-MG3Z	Approved	[2]
Pruritus	EC90	Phase 3	[3]
Respiratory depression	MD11.5	Phase 3	[4]
Opioid dependence	6C43.2Z	Phase 1	[4]
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Therapeutic Class

Antinarcotic Agents

Affected Organisms

Humans and other mammals

ATC Code

A06AH04: Naloxone

A06AH: Peripheral opioid receptor antagonists

A06A: DRUGS FOR CONSTIPATION

A06: DRUGS FOR CONSTIPATION

A: ALIMENTARY TRACT AND METABOLISM

V03AB15: Naloxone

V03AB: Antidotes

V03A: ALL OTHER THERAPEUTIC PRODUCTS

V03: ALL OTHER THERAPEUTIC PRODUCTS

V: VARIOUS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

327.4

Logarithm of the Partition Coefficient (xlogp)

2.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 16.7-19.0 mcgh/L [5]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 12.3-12.8 mcg/L [5]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.25 h [5]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [6]
Bioavailability: The bioavailability of drug is 42-47% [5]
Clearance: The clearance of drug is 2500 L/day [7]
Elimination: After oral or intravenous administration, naloxone is 25-40% eliminated in the urine within 6 hours, 50% in 24 hours, and 60-70% in 72 hours [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.8 - 2.7 hours [8]
Metabolism: The drug is metabolized via the glucuronidation to form naloxone-3-glucuronide [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.30545 micromolar/kg/day [9]
Unbound Fraction: The unbound fraction of drug in plasma is 0.54% [10]
Vd: The volume of distribution (Vd) of drug is 200 L [7]

Chemical Identifiers

Formula: C19H21NO4
IUPAC Name: (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
Canonical SMILES: C=CCN1CC[C@]23[C@@H]4C(=O)CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O
InChI: InChI=1S/C19H21NO4/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h2-4,14,17,21,23H,1,5-10H2/t14-,17+,18+,19-/m1/s1
InChIKey: UZHSEJADLWPNLE-GRGSLBFTSA-N

Cross-matching ID

PubChem CID: 5284596
ChEBI ID: CHEBI:7459
CAS Number: 465-65-6
UNII: 36B82AMQ7N
DrugBank ID: DB01183
TTD ID: D0X3FX
VARIDT ID: DR00698

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
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Antagonist	[11]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Gene/Protein Processing	[12]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Protein Interaction/Cellular Processes	[13]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Protein Interaction/Cellular Processes	[14]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Protein Interaction/Cellular Processes	[15]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Gene/Protein Processing	[16]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Gene/Protein Processing	[17]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Gene/Protein Processing	[18]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Gene/Protein Processing	[19]
Renin (REN)	OT52GZR2	RENI_HUMAN	Gene/Protein Processing	[20]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Biotransformations	[21]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Narcotic depression

ICD Disease Classification

6A7Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor mu (MOP)	DTT	OPRM1	5.94E-01	-0.02	-0.17

Molecular Expression Atlas (MEA)

MEA Detail

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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: 1668).
2	Naloxone FDA Label
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	FDA Approved Drug Products: Kloxxado (Naloxone) Nasal Spray
6	BDDCS applied to over 900 drugs
7	Rzasa Lynn R, Galinkin JL: Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018 Jan;9(1):63-88. doi: 10.1177/2042098617744161. Epub 2017 Dec 13.
8	Caymen Chemical: Naloxone MSDS
9	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
10	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
11	OxyContin abuse and overdose. Postgrad Med. 2009 Mar;121(2):163-7.
12	Chronic oxycodone induces integrated stress response in rat brain. BMC Neurosci. 2015 Sep 16;16:58. doi: 10.1186/s12868-015-0197-8.
13	Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009 May 20;29(20):6449-60. doi: 10.1523/JNEUROSCI.0708-09.2009.
14	Interleukin-2-induced antinociception in morphine-insensitive rats. Acta Pharmacol Sin. 2002 Nov;23(11):981-4.
15	Human carboxylesterase 1: from drug metabolism to drug discovery. Biochem Soc Trans. 2003 Jun;31(Pt 3):620-4. doi: 10.1042/bst0310620.
16	Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
17	Opioid peptides attenuate blood pressure increase in acute respiratory failure. Peptides. 2001 Apr;22(4):631-7. doi: 10.1016/s0196-9781(01)00373-4.
18	Endogenous opioids modulate the cardiovascular response to mental stress. Psychoneuroendocrinology. 1990;15(3):185-92. doi: 10.1016/0306-4530(90)90029-9.
19	Influence of naloxone on muscle sympathetic nerve activity, systemic and calf haemodynamics and ambulatory blood pressure after exercise in mild essential hypertension. J Hypertens. 1995 Apr;13(4):447-61.
20	beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
21	Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.