DIAMORPHINE

First marketed in 1827

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H23NO5
Molecular Weight	369.411
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12OC3=C4C(C[C@@]5([H])N(C)CC[C@@]14[C@@]5([H])C=C[C@@H]2OC(C)=O)=CC=C3OC(C)=O

InChI

InChIKey=GVGLGOZIDCSQPN-PVHGPHFFSA-N

InChI=1S/C21H23NO5/c1-11(23)25-16-6-4-13-10-15-14-5-7-17(26-12(2)24)20-21(14,8-9-22(15)3)18(13)19(16)27-20/h4-7,14-15,17,20H,8-10H2,1-3H3/t14-,15+,17-,20-,21-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C21H23NO5
Molecular Weight	369.411
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 2678
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 2678
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 2678

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 8429	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

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 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	CYP1A2 1054 CYP2C19 991 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2E1 667 UGT2B7 389 UGT1A1 418 UGT1A3 422 UGT1A6 307 UGT1A8 283 UGT1A9 380 UGT1A10 291 OCT1 327 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1650	inhibitor 3277 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no
P-gp 1650	inhibitor 3277 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-3-glucuronide 26
P-gp 1650	inhibitor 3277 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 1054	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2A6 543	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2B6 664	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2E1 667	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 10100 uM]
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 12600 uM]
CYP3A4 1737	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 14150 uM]
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18000 uM]
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18700 uM]
CYP2C9 1037	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 25400 uM]
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 2600 uM]
OCT1 327	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295213003900 Page: -	yes [Km 3.4 uM]
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 3200 uM]
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 37400 uM]
UGT2B7 389	substrate 3367 Sources: https://molpharm.aspetjournals.org/content/67/3/665.short Page: -	yes [Km 380 uM]
CYP2C8 693	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 4800 uM]
CYP2C19 991	substrate 3367 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 6400 uM]
P-gp 1537	substrate 3367 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes
P-gp 1537	substrate 3367 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-3-glucuronide 26
P-gp 1537	substrate 3367 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
Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine.	1978 Sep 15	100809
Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction.	1998 Dec	10070497
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
Extrapyramidal side-effects from droperidol mixed with morphine for patient-controlled analgesia in two children.	1999	10411778
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
[Opioid receptor knockout mice].	1999 Dec	10803207
Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat.	1999 Feb 26	10096766
[The discriminative stimulus properties of naloxone during dissociative learning in a Y maze in morphine-dependent rats].	1999 Jan-Feb	10330710
Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice.	1999 Jul 14	10448923
Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.	1999 Mar	10642972
Intra-articular morphine for pain relief after knee arthroscopy.	1999 Mar	10081529
Controlling myoclonus after high-dosage morphine infusions.	1999 May 15	10365727
Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice.	1999 Sep	10495006
Morphine inhibits human microglial cell production of, and migration towards, RANTES.	2000	11106302
Nonconvulsive status epilepticus: the role of morphine and its antagonist.	2000 Apr	10812579
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
Preemptive intravenous morphine-6-glucuronide is ineffective for postoperative pain relief.	2000 Feb	10691220
Influence of morphine treatment in pregnant rats on the mineralocorticoid activity of the adrenals in their neonates.	2000 Feb 18	10737415
Previous cholecystectomy and choledochal sphincter spasm after morphine sedation.	2000 Jan	10626719
Orphanin FQ/nociceptin inhibits morphine withdrawal.	2000 Jan 14	10680585
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
Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta.	2000 May	10809959
Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence.	2000 Oct 15	11027224
Inhaled morphine to relieve dyspnea in advanced cystic fibrosis lung disease.	2000 Sep	10973044
mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia.	2001	11077066
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
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
Ketorolac reduces postoperative narcotic requirements.	2001 Jan	11150441
Morphine nerve paste.	2001 Jan	11147863
Opiates, intracranial pressure, and autoregulation.	2001 Jan	11135743
Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age.	2001 Jan	11134442
The combined effects of N-type calcium channel blockers and morphine on A delta versus C fiber mediated nociception.	2001 Jan	11133635
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
Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme.	2001 Jan	11125020
Sublingual morphine may be a suitable alternative for pain control in children in the postoperative period.	2001 Jan	11123737
Morphine with or without a local anaesthetic for postoperative intrathecal pain treatment after selective dorsal rhizotomy in children.	2001 Jan	11123736
Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice.	2001 Jan	11123356
Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance.	2001 Jan 1	11150345
Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia.	2001 Jan 5	11146054
Occurrence of morphine tolerance and dependence in the nucleus paragigantocellularis neurons.	2001 Jan 5	11137862

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 `Fri Dec 15 14:59:58 GMT 2023` Edited by `admin` on `Fri Dec 15 14:59:58 GMT 2023`
Record UNII	70D95007SX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIAMORPHINE

Common Name

English

DIAPHORM

Common Name

English

DIAMORPHINE-

Common Name

English

DIACETYLMORPHINE

Common Name

English

DIACETYLMORPHINE [MI]

Common Name

English

IDS-NH-001(SECT.3)

Code

English

ECLORION

Common Name

English

HEROIN [HSDB]

Common Name

English

Diamorphine [WHO-DD]

Common Name

English

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

Common Name

English

CHINA WHITE

Common Name

English

HEROIN

Common Name

English

IDS-NH-001

Code

English

J6.494G

Code

English

ACETOMORPHINE

Common Name

English

MORPHACETIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

N07BC06