NALORPHINE HYDROCHLORIDE

US Previously Marketed

First approved in 1952

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H21NO3.ClH
Molecular Weight	347.836
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]12OC3=C4C(C[C@H]5N(CC=C)CC[C@@]14[C@@]5([H])C=C[C@@H]2O)=CC=C3O

InChI

InChIKey=NAHATSPWSULUAA-ZQGPYOJVSA-N

InChI=1S/C19H21NO3.ClH/c1-2-8-20-9-7-19-12-4-6-15(22)18(19)23-17-14(21)5-3-11(16(17)19)10-13(12)20;/h2-6,12-13,15,18,21-22H,1,7-10H2;1H/t12-,13+,15-,18-,19-;/m0./s1

HIDE SMILES / InChI

Description
Sources: http://en.medicine-cure.com/ovr4_nalorfin.htm
Curator's Comment: description was created based on several sources, including: http://en.pharmacodia.com/web/drug/1_12280.html | https://www.ncbi.nlm.nih.gov/pubmed/16433932 | https://www.ncbi.nlm.nih.gov/pubmed/6301606 | doi:10.3181/00379727-77-18904

Nalorphine has a mixed opioid agonist-antagonist properties. Nalorphine inhibits the cholinesterases of mouse brain, bovine erythrocytes and horse serum. It acts on mu-, k- and sigma-opioid receptors. Nalorfin by virtue of the agonistic effect has an analgesic effect but to a much lesser extent than morphine. Initially, before the appearance of a "pure" morphine-naloxone antagonist, nalorphine was used as an antidote for severe respiratory depression and other body function disorders caused by acute poisoning in case of an overdose of morphine, promedol, fentanyl or other narcotic analgesics, or with increased sensitivity to them. At present, nalorphine is practically not used for this purpose. It was replaced by naloxone. Large doses of nalorphine can cause nausea, cramps, drowsiness, headache, mental stimulation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 207 Target ID: CHEMBL3198 Sources: doi: 10.3181/00379727-77-18904	Inhibitor 8297
Kappa opioid receptor 108 Target ID: CHEMBL4329 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16433932	Agonist 2678	1.6 nM [Ki]
Mu opioid receptor 221 Target ID: CHEMBL270 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8819494	Partial Agonist 290
Sigma opioid receptor 63 Target ID: CHEMBL3602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6301606	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Opioid overdose 2 Sources: http://en.medicine-cure.com/ovr4_nalorfin.htm	Secondary		Approved 8429	Norfin Approved Use It is used as an antidote for opiates.

C_max

Value	Dose	Co-administered	Analyte	Population
1.12 μg/g REVIEW https://www.springer.com/gp/book/9781468418712	2 mg/kg single, subcutaneous dose: 2 mg/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NALORPHINE unknown	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.17 μg × h/g REVIEW https://www.springer.com/gp/book/9781468418712	2 mg/kg single, subcutaneous dose: 2 mg/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NALORPHINE unknown	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
23 min REVIEW https://www.springer.com/gp/book/9781468418712	2 mg/kg single, subcutaneous dose: 2 mg/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NALORPHINE unknown	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	SULT1A1 29 SULT1A3 27 SULT1E1 17 SULT2A1 24 UGT2B1 14

Drug as victim

Target	Modality	Activity
SULT1A1 29	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459640/	major
SULT1E1 17	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459640/	not detected
SULT1A3 27	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459640/	yes
SULT2A1 24	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459640/	yes
UGT2B1 14	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9029056/	yes

Sourcing

Vendor/Aggregator	ID	URL
Alsachim	3976	http://www.alsachim.com/product-C5281-glo.bal-view.html
ChemMol	99117845	http://www.chemmol.com/chemmol/99117845.html
Chemieliva Pharmaceutical Co., Ltd	PBCM1361788
Compound Cloud	5284595
Compound Cloud	5484366
NovoSeek	5284595
Sigma Aldrich	1452002
Sigma Aldrich	1452002\|USP
Sigma Aldrich	N-924
Sigma Aldrich	N0762
Sigma Aldrich	N0762\|SIGMA
Toronto Research Chemicals	KIT6360
Toronto Research Chemicals	N284450
ZINC	ZINC000003875420	http://zinc15.docking.org/substances/ZINC000003875420
eMolecules	260189857

PubMed

Title	Date	PubMed
Changes in nalorphine-induced hyperprolactinaemia after bromocriptine or sulpiride administration.	1982	7106173
Activation of the cloned human kappa opioid receptor by agonists enhances [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of ligands.	1997 Aug	9262330
Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.	1998 Mar	9686407

Patents

Sample Use Guides

In Vivo Use Guide

Adults appoint 0,005 - 0,01 g (1 - 2 ml of a 0.5% solution). If the effect is insufficient, the injections are repeated at intervals of 10 to 15 minutes. The total dose should not exceed 0.04 g (8 ml of 0.5% solution).

Route of Administration: Other

In Vitro Use Guide

Maximum stimulation of [35S]GTPyS binding by Nalorphine using a single saturating concentration of ligand (10 uM) was compared with stimulation by DAAMGO (10 uM). Intrinsic activity determined for Nalorphine in C6 glioma cells was 9%.

Name

Type

Language

NALORPHINE HYDROCHLORIDE

Common Name

English

NALORPHINE HCL

Common Name

English

17-Allyl-7,8-didehydro-4,5α-epoxymorphinan-3,6α-diol hydrochloride

Systematic Name

English

NALORPHINE HYDROCHLORIDE CIII

Common Name

English

MORPHINAN-3,6-DIOL, 7,8-DIDEHYDRO-4,5-EPOXY-17-(2-PROPENYL)-(5.ALPHA.,6.ALPHA.)-, HYDROCHLORIDE

Systematic Name

English

NALORPHINE HYDROCHLORIDE [MART.]

Common Name

English

Nalorphine hydrochloride [WHO-DD]

Common Name

English

NALORPHINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

NALORPHINE HYDROCHLORIDE [GREEN BOOK]

Common Name

English

NALORPHINE HYDROCHLORIDE CIII [USP-RS]

Common Name

English

NALORPHINE HYDROCHLORIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67413