MORPHINE NITRATE

First marketed in 1827

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H19NO3.HNO3
Molecular Weight	348.3505
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[N+]([O-])=O.[H][C@@]12OC3=C(O)C=CC4=C3[C@@]15CCN(C)[C@H](C4)[C@]5([H])C=C[C@@H]2O

InChI

InChIKey=VHBDDUMTLJSZDR-VYKNHSEDSA-N

InChI=1S/C17H19NO3.HNO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18;2-1(3)4/h2-5,10-11,13,16,19-20H,6-8H2,1H3;(H,2,3,4)/t10-,11+,13-,16-,17-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C17H19NO3
Molecular Weight	285.3377
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	HNO3
Molecular Weight	63.0128
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018565s022lbl_Duramorph.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16530171

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16580639	Agonist 2662
Kappa-type opioid receptor 60 Target ID: P41145 Gene ID: 4986.0 Gene Symbol: OPRK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16530171	Agonist 2662
Delta-type opioid receptor 45 Target ID: P41143 Gene ID: 4985.0 Gene Symbol: OPRD1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10670411	Agonist 2662

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain severe 26 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018565s022lbl_Duramorph.pdf	Palliative		Approved 8360	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 4.64313614E11

C_max

Value	Dose	Co-administered	Analyte	Population
63 nM EXPERIMENT https://link.springer.com/article/10.2165/00003088-199324040-00007	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

Value	Dose	Co-administered	Analyte	Population
165 nM × h EXPERIMENT https://link.springer.com/article/10.2165/00003088-199324040-00007	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
15.1 h EXPERIMENT https://link.springer.com/article/10.2165/00003088-199324040-00007	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
65% EXPERIMENT https://link.springer.com/article/10.2165/00003088-199324040-00007	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

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2720580/	healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/2720580/	Sources: https://pubmed.ncbi.nlm.nih.gov/2720580/
180 mg 1 times / day steady, oral Dose: 180 mg, 1 times / day Route: oral Route: steady Dose: 180 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28530786/	unhealthy, adult n = 152 Health Status: unhealthy Condition: neuropathic pain Age Group: adult Sex: unknown Population Size: 152 Sources: https://pubmed.ncbi.nlm.nih.gov/28530786/	Sources: https://pubmed.ncbi.nlm.nih.gov/28530786/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437	CYP1A2 1032 CYP2C19 985 CYP2A6 523 CYP2B6 660 CYP2C8 688 CYP2E1 648 UGT2B7 389 UGT1A1 418 UGT1A3 422 UGT1A6 307 UGT1A8 283 UGT1A9 380 UGT1A10 290 OCT1 322 P-gp 1527

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1626	inhibitor 3240 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no
P-gp 1626	inhibitor 3240 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-3-glucuronide 26
P-gp 1626	inhibitor 3240 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-6-glucuronide 26

Drug as victim

Target	Modality	Activity	Metabolite
CYP1A2 1032	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2A6 523	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2B6 660	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2E1 648	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2D6 1193	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 10100 uM]
UGT1A10 290	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 12600 uM]
CYP3A4 1709	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 14150 uM]
UGT1A6 307	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18000 uM]
UGT1A1 418	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18700 uM]
CYP2C9 1010	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 25400 uM]
UGT1A8 283	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 2600 uM]
OCT1 322	substrate 3326 Sources: https://www.sciencedirect.com/science/article/pii/S0006295213003900 Page: -	yes [Km 3.4 uM]
UGT1A3 422	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 3200 uM]
UGT1A9 380	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 37400 uM]
UGT2B7 389	substrate 3326 Sources: https://molpharm.aspetjournals.org/content/67/3/665.short Page: -	yes [Km 380 uM]
CYP2C8 688	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 4800 uM]
CYP2C19 985	substrate 3326 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 6400 uM]
P-gp 1527	substrate 3326 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes
P-gp 1527	substrate 3326 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-3-glucuronide 26
P-gp 1527	substrate 3326 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-6-glucuronide 26

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:17303	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:17303
ZINC	ZINC000003812983	http://zinc15.docking.org/substances/ZINC000003812983
eMolecules	6843460	https://www.emolecules.com/cgi-bin/more?vid=6843460

PubMed

Title	Date	PubMed
[Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms].	1997 Jan	10921076
Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine.	1998 Dec 1	10933337
Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.	1999	10907730
Efficacy and complications of morphine infusions in postoperative paediatric patients.	1999	10411768
The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment.	1999 Apr	10323593
[The discriminative stimulus properties of naloxone during dissociative learning in a Y maze in morphine-dependent rats].	1999 Jan-Feb	10330710
Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.	1999 Mar	10642972
Controlling myoclonus after high-dosage morphine infusions.	1999 May 15	10365727
Patient-controlled analgesia with morphine plus lysine acetyl salicylate.	1999 Oct	10512278
Morphine inhibits human microglial cell production of, and migration towards, RANTES.	2000	11106302
Peroperative titration of morphine improves immediate postoperative analgesia after total hip arthroplasty.	2000 Apr	10764173
Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum.	2000 Apr 14	10814832
The effects of intrathecal morphine encapsulated in L- and D-dipalmitoylphosphatidyl choline liposomes on acute nociception in rats.	2000 Aug	10910861
The effect of spinal ibuprofen on opioid withdrawal in the rat.	2000 Aug	10910860
The development of pain-related behaviour and opioid tolerance after neuropathy-inducing surgery and sham surgery.	2000 Dec 1	11068110
Reversal of morphine-induced apnea in the anesthetized rat by drugs that activate 5-hydroxytryptamine(1A) receptors.	2000 Feb	10640309
Orphanin FQ/nociceptin inhibits morphine withdrawal.	2000 Jan 14	10680585
Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction.	2000 Jul	10964147
Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain.	2000 Jul	10840460
Pethidine reverses morphine-induced delirium.	2000 Jun	10853216
Prenatal morphine exposure enhances seizure susceptibility but suppresses long-term potentiation in the limbic system of adult male rats.	2000 Jun 30	10865073
Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice.	2000 May	10867961
Lack of specific effects of selective D(1) and D(2) dopamine antagonists vs. risperidone on morphine-induced hyperactivity.	2000 May	10837860
Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta.	2000 May	10809959
Insidious intoxication after morphine treatment in renal failure: delayed onset of morphine-6-glucuronide action.	2000 May	10781294
Inhaled morphine to relieve dyspnea in advanced cystic fibrosis lung disease.	2000 Sep	10973044
Downbeat nystagmus associated with intravenous patient-controlled administration of morphine.	2000 Sep	10960401
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.	2001 Apr	11137626
Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery.	2001 Feb	11159249
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.	2001 Feb	11158213
Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures.	2001 Feb 3	11157525
Knockdown of spinal metabotropic glutamate receptor 1 (mGluR(1)) alleviates pain and restores opioid efficacy after nerve injury in rats.	2001 Jan	11156596
Contralateral but not systemic administration of the kappa-opioid agonist U-50,488H induces anti-nociception in acute hindpaw inflammation in rats.	2001 Jan	11156584
Comparison of three methods to find the vapor activity of a hydration step.	2001 Jan	11154907
Cellular and synaptic adaptations mediating opioid dependence.	2001 Jan	11152760
Circuitry underlying antiopioid actions of cholecystokinin within the rostral ventromedial medulla.	2001 Jan	11152727
Ketorolac reduces postoperative narcotic requirements.	2001 Jan	11150441
Early serial EEG in hypoxic ischaemic encephalopathy.	2001 Jan	11137658
Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age.	2001 Jan	11134442
A prospective survey of patients after cessation of patient-controlled analgesia.	2001 Jan	11133632
Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes.	2001 Jan	11133627
A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain.	2001 Jan	11133596
Parental perceptions of comfort during mechanical ventilation.	2001 Jan	11123740
Sublingual morphine may be a suitable alternative for pain control in children in the postoperative period.	2001 Jan	11123737
Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice.	2001 Jan	11123356
Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal.	2001 Jan	11106878
Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance.	2001 Jan 1	11150345
Occurrence of morphine tolerance and dependence in the nucleus paragigantocellularis neurons.	2001 Jan 5	11137862
Morphine induces short-lived changes in G-protein gene expression in rat prefrontal cortex.	2001 Jan 5	11137853
Effect of organic cations on the renal tubular secretion of pseudoephedrine in the rat.	2001 Jan-Feb	11153535

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Thu Jul 06 15:46:12 UTC 2023` Edited by `admin` on `Thu Jul 06 15:46:12 UTC 2023`
Record UNII	DV2P23JCWV
Record Status	`Validated (UNII)`
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Name

Type

Language

MORPHINE NITRATE

Common Name

English

MORPHINAN-3,6-DIOL, 7,8-DIDEHYDRO-4,5-EPOXY-17-METHYL- (5.ALPHA.,6.ALPHA.)-, NITRATE (SALT)

Common Name

English

MORPHINAN-3,6-DIOL, 7,8-DIDEHYDRO-4,5-EPOXY-17-METHYL- (5.ALPHA.,6.ALPHA.)-, NITRATE (1:1)

Systematic Name

English

Code System Code Type Description

PUBCHEM

66722023