MORPHINE

First marketed in 1827

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H19NO3
Molecular Weight	285.3377
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=BQJCRHHNABKAKU-KBQPJGBKSA-N

InChI=1S/C17H19NO3/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/h2-5,10-11,13,16,19-20H,6-8H2,1H3/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

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
Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs.	1976 Aug	10058
The importance of the number of NMDA receptors in the development of supersensitivity or tolerance to and dependence on morphine.	1999 Apr	10208762
Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine).	1999 Aug 25	10521585
Prenatal morphine exposure differentially alters seizure susceptibility in developing female rats.	1999 Aug 5	10446353
Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.	1999 Mar	10642972
Sleep impairments in rats implanted with morphine pellets.	1999 Nov	10559705
Patient-controlled analgesia with morphine plus lysine acetyl salicylate.	1999 Oct	10512278
Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice.	1999 Sep	10495006
Morphine induced allodynia in a child with brain tumour.	1999 Sep 4	10473483
Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum.	2000 Apr 14	10814832
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
Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta.	2000 May	10809959
Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects.	2000 Sep	10960384
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
Comparison of three methods to find the vapor activity of a hydration step.	2001 Jan	11154907
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
Morphine with or without a local anaesthetic for postoperative intrathecal pain treatment after selective dorsal rhizotomy in children.	2001 Jan	11123736
Occurrence of morphine tolerance and dependence in the nucleus paragigantocellularis neurons.	2001 Jan 5	11137862
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 00:01:05 UTC 2023` Edited by `admin` on `Thu Jul 06 00:01:05 UTC 2023`
Record UNII	76I7G6D29C
Record Status	`Validated (UNII)`
Record Version

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Related Record	Type

Name

Type

Language

MORPHINE

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CODEINE PHOSPHATE SESQUIHYDRATE IMPURITY B [EP IMPURITY]

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CODEINE MONOHYDRATE IMPURITY B [EP IMPURITY]

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HYDROCODONE HYDROGEN TARTRATE 2.5-HYDRATE IMPURITY A [EP IMPURITY]

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DIHYDROCODEINE HYDROGEN TARTRATE IMPURITY B [EP IMPURITY]

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

Common Name

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MORPHINE [VANDF]

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MORPHIA

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DUROMORPH

Common Name

English

ANHYDROUS MORPHINE

Common Name

English

MORPHINE [HSDB]

Common Name

English

MORPHINE EXTENDED RELEASE

Common Name

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OSPALIVINA

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MORPHINE [MI]

Common Name

English

N02AA01

Code

English

4,5.ALPHA.-EPOXY-17-METHYL-7,8-DIDEHYDROMORPHINAN-3,6.ALPHA.-DIO

Systematic Name

English

(5.ALPHA.,6.ALPHA.)-7,8-DIDEHYDRO-4,5-EPOXY-17-METHYLMORPHINAN-3,6-DIOL

Systematic Name

English

7,8-DIDEHYDRO-4,5.ALPHA.-EPOXY-17-METHYLMORPHINAN-3,6.ALPHA.-DIOL

Systematic Name

English

APOMORPHINE HYDROCHLORIDE HEMIHYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

HYDROMORPHONE HYDROCHLORIDE IMPURITY, MORPHINE- [USP IMPURITY]

Common Name

English

7,8-didehydro-4,5α-epoxy-17-methylmorphinan-3,6α-diol

Systematic Name

English

CODEINE PHOSPHATE HEMIHYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

CODEINE HYDROCHLORIDE DIHYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

MORPHINE (ANHYDROUS) [VANDF]

Common Name

English

Morphine [WHO-DD]

Common Name

English

ETHYLMORPHINE HYDROCHLORIDE IMPURITY B [EP IMPURITY]

Common Name

English

IDS-NM-009

Code

English

HYDROMORPHONE HYDROCHLORIDE IMPURITY C [EP IMPURITY]

Common Name

English

MORPHINE (ANHYDROUS)

Common Name

English

MORPHINE ANHYDROUS

Common Name

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

8.4