U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H22NO3.Cl
Molecular Weight 335.825
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MORPHINE METHYLCHLORIDE

SMILES

[Cl-].[H][C@]12OC3=C4C(C[C@]5([H])[C@]([H])(C=C[C@@H]1O)[C@]24CC[N+]5(C)C)=CC=C3O

InChI

InChIKey=MJNCZWBHCFTYFU-SCLAZZCHSA-N
InChI=1S/C18H21NO3.ClH/c1-19(2)8-7-18-11-4-6-14(21)17(18)22-16-13(20)5-3-10(15(16)18)9-12(11)19;/h3-6,11-12,14,17,21H,7-9H2,1-2H3;1H/t11-,12+,14-,17-,18-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C18H21NO3
Molecular Weight 299.3642
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Morphine is one of the most important and widely used opioid for the treatment of chronic and acute pain: the very wide interindividual variability in the patients’ response to the drug may have genetic derivations. Sulphate salt of morphine sold under the many brand names, one of them, DURAMORPH, which is indicated for the management of pain severe enough to require use of an opioid analgesic by intravenous administration, and for which alternative treatments are not expected to be adequate. In addition for the epidural or intrathecal management of pain without attendant loss of motor, sensory, or sympathetic function. Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Morphine has a high potential for addiction and abuse. Common side effects include drowsiness, vomiting, and constipation. Caution is advised when used during pregnancy or breast-feeding, as morphine will affect the baby.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P41145
Gene ID: 4986.0
Gene Symbol: OPRK1
Target Organism: Homo sapiens (Human)
Target ID: P41143
Gene ID: 4985.0
Gene Symbol: OPRD1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
DURAMORPH PF

Approved Use

DURAMORPH is indicated for: the management of pain severe enough to require use of an opioid analgesic by intravenous administration, and for which alternative treatments are not expected to be adequate.For the epidural or intrathecal management of pain without attendant loss of motor, sensory, or sympathetic function.

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
63 nM
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MORPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
165 nM × h
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MORPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.1 h
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MORPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
65%
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MORPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: unknown
Sources:
180 mg 1 times / day steady, oral
Dose: 180 mg, 1 times / day
Route: oral
Route: steady
Dose: 180 mg, 1 times / day
Sources:
unhealthy, adult
n = 152
Health Status: unhealthy
Condition: neuropathic pain
Age Group: adult
Sex: unknown
Population Size: 152
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
yes [Km 10100 uM]
yes [Km 12600 uM]
yes [Km 14150 uM]
yes [Km 18000 uM]
yes [Km 18700 uM]
yes [Km 25400 uM]
yes [Km 2600 uM]
yes [Km 3.4 uM]
yes [Km 3200 uM]
yes [Km 37400 uM]
yes [Km 380 uM]
yes [Km 4800 uM]
yes [Km 6400 uM]
yes
yes
yes
PubMed

PubMed

TitleDatePubMed
Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs.
1976 Aug
Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine.
1978 Sep 15
[Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms].
1997 Jan
Epidural analgesia in children with cerebral palsy.
1998 Dec
Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.
1999
Extrapyramidal side-effects from droperidol mixed with morphine for patient-controlled analgesia in two children.
1999
[Transverse myelopathy as a complication following long-term intrathecal application of morphine in chronic back pain].
1999 Aug
[Opioid receptor knockout mice].
1999 Dec
The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.
1999 May
Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice.
1999 Sep
Potentiation of narcosis after intravenous lidocaine in a patient given spinal opioids.
1999 Sep
Morphine induced allodynia in a child with brain tumour.
1999 Sep 4
A comparison of continuous epidural infusion and intermittent intravenous bolus doses of morphine in children undergoing selective dorsal rhizotomy.
1999 Sep-Oct
Nonconvulsive status epilepticus: the role of morphine and its antagonist.
2000 Apr
Peroperative titration of morphine improves immediate postoperative analgesia after total hip arthroplasty.
2000 Apr
Intrathecal morphine suppresses NK cell activity following abdominal surgery.
2000 Apr
Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum.
2000 Apr 14
The effects of intrathecal morphine encapsulated in L- and D-dipalmitoylphosphatidyl choline liposomes on acute nociception in rats.
2000 Aug
The effect of spinal ibuprofen on opioid withdrawal in the rat.
2000 Aug
Apnoea with intrathecal morphine.
2000 Dec
Influence of morphine treatment in pregnant rats on the mineralocorticoid activity of the adrenals in their neonates.
2000 Feb 18
Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction.
2000 Jul
Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice.
2000 May
Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta.
2000 May
Insidious intoxication after morphine treatment in renal failure: delayed onset of morphine-6-glucuronide action.
2000 May
Systemic naloxone enhances cerebral blood flow in anesthetized morphine-dependent rats.
2000 Nov 24
Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence.
2000 Oct 15
Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects.
2000 Sep
Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery.
2001 Feb
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.
2001 Feb
Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures.
2001 Feb 3
Contralateral but not systemic administration of the kappa-opioid agonist U-50,488H induces anti-nociception in acute hindpaw inflammation in rats.
2001 Jan
Comparison of three methods to find the vapor activity of a hydration step.
2001 Jan
Circuitry underlying antiopioid actions of cholecystokinin within the rostral ventromedial medulla.
2001 Jan
Buprenorphine substitution ameliorates spontaneous withdrawal in fentanyl-dependent rat pups.
2001 Jan
A prospective survey of patients after cessation of patient-controlled analgesia.
2001 Jan
Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes.
2001 Jan
Morphine with or without a local anaesthetic for postoperative intrathecal pain treatment after selective dorsal rhizotomy in children.
2001 Jan
Heroin-related deaths in Victoria: a review of cases for 1997 and 1998.
2001 Jan 1
Morphine induces short-lived changes in G-protein gene expression in rat prefrontal cortex.
2001 Jan 5
Effect of organic cations on the renal tubular secretion of pseudoephedrine in the rat.
2001 Jan-Feb
Patents

Sample Use Guides

Dosage for Intravenous Administration: Adult Dosage: The initial dose of morphine should be 2 mg to 10 mg/70 kg of body weight. Dosage for Epidural Administration: Adult Dosage: Initial injection of 5 mg in the lumbar region may provide satisfactory pain relief for up to 24 hours. If adequate pain relief is not achieved within one hour, careful administration of incremental doses of 1 to 2 mg at intervals sufficient to assess effectiveness may be given. Do not administer more than 10 mg per 24 hours. Dosage for Intrathecal Administration: Adult Dosage: Intrathecal dosage is usually 1/10 that of epidural dosage. A single injection of 0.2 to 1 mg may provide satisfactory pain relief for up to 24 hours. (Caution: this is only 0.4 to 2 mL of the 5 mg/10 mL ampul or 0.2 to 1 mL of the 10 mg/10 mL ampul of DURAMORPH). Do not inject intrathecally more than 2 mL of the 5 mg/10 mL ampul or 1 mL of the 10 mg/10 mLampul. Repeated intrathecal injections of DURAMORPH are not recommended. If pain recurs, consider consider alternative routes of administration.
Route of Administration: Other
It was evaluated the effect of morphine on the proangiogenic interaction taking place between macrophages and breast cancer cells in vitro. It was shown, that morphine prevents, in part via modulating VEGF-A expression, the pro-angiogenic interaction between macrophages and breast cancer cells. The conditioned medium (CM) from breast cancer cells co-cultured with macrophages elicited endothelial cell proliferation and tube formation. This effect was inhibited if the co-culture occurred in the presence of morphine (20 uM). Using a mouse antibody array, it was identified several angiogenesis-regulating factors differentially expressed in the CM of co-cultured cells prepared in the presence or absence of morphine (o, 10, 20 uM), amongst which interleukin (IL)-6, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A. VEGF was induced in both cell types by the co-culture and this was prevented by morphine in a non-naloxone reversible fashion. The effect of CM from co-cultured cells on endothelial tube formation, but not proliferation, was prevented by anti-VEGF neutralizing antibody
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:57:16 GMT 2023
Edited
by admin
on Sat Dec 16 01:57:16 GMT 2023
Record UNII
D74B54D2RE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MORPHINE METHYLCHLORIDE
Common Name English
MORPHINANIUM, 7,8-DIDEHYDRO-4,5.ALPHA.-EPOXY-3,6.ALPHA.-DIHYDROXY-17,17-DIMETHYL-, CHLORIDE
Systematic Name English
MORPHINANIUM, 7,8-DIDEHYDRO-4,5-EPOXY-3,6-DIHYDROXY-17,17-DIMETHYL-, CHLORIDE (1:1), (5.ALPHA.,6.ALPHA.)-
Systematic Name English
N-METHYLMORPHINE CHLORIDE
Common Name English
(4R,4AR,7S,7AR,12BS)-3,3-DIMETHYL-2,4,4A,7,7A,13-HEXAHYDRO-1H-4,12-METHANOBENZOFURO(3,2-E)ISOQUINOLINE-3-IUM-7,9-DIOL CHLORIDE
Systematic Name English
5.7,8-DIDEHYDRO-4,5-EPOXY-3,6-DIHYDROXY-17,17-DIMETHYLMORPHINANIUM CHLORIDE, (5ALPHA,6ALPHA)-
Systematic Name English
(5.ALPHA.,6.ALPHA.)-3,6-DIHYDROXY-17,17-DIMETHYL-7,8-DIDEHYDRO-4,5-EPOXYMORPHINAN-17-IUM CHLORIDE
Systematic Name English
N-METHYLMORPHINIUM CHLORIDE
Common Name English
Code System Code Type Description
PUBCHEM
5492950
Created by admin on Sat Dec 16 01:57:16 GMT 2023 , Edited by admin on Sat Dec 16 01:57:16 GMT 2023
PRIMARY
FDA UNII
D74B54D2RE
Created by admin on Sat Dec 16 01:57:16 GMT 2023 , Edited by admin on Sat Dec 16 01:57:16 GMT 2023
PRIMARY
EPA CompTox
DTXSID60930915
Created by admin on Sat Dec 16 01:57:16 GMT 2023 , Edited by admin on Sat Dec 16 01:57:16 GMT 2023
PRIMARY
CAS
14075-02-6
Created by admin on Sat Dec 16 01:57:16 GMT 2023 , Edited by admin on Sat Dec 16 01:57:16 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> DERIVATIVE
SALT/SOLVATE -> PARENT
PARENT -> SALT/SOLVATE