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

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 2637
Kappa-type opioid receptor 59 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 2637
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 2637

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 8307	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 1670	substrate 985	substrate 1168

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1401	CYP1A2 1013 CYP2C19 955 CYP2A6 510 CYP2B6 648 CYP2C8 670 CYP2E1 633 UGT2B7 387 UGT1A1 417 UGT1A3 421 UGT1A6 306 UGT1A8 282 UGT1A9 378 UGT1A10 289 OCT1 317 P-gp 1491

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1588	inhibitor 3185 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no
P-gp 1588	inhibitor 3185 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-3-glucuronide 26
P-gp 1588	inhibitor 3185 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 1013	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2A6 510	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2B6 648	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2E1 633	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2D6 1168	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 10100 uM]
UGT1A10 289	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 12600 uM]
CYP3A4 1670	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 14150 uM]
UGT1A6 306	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18000 uM]
UGT1A1 417	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18700 uM]
CYP2C9 985	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 25400 uM]
UGT1A8 282	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 2600 uM]
OCT1 317	substrate 3264 Sources: https://www.sciencedirect.com/science/article/pii/S0006295213003900 Page: -	yes [Km 3.4 uM]
UGT1A3 421	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 3200 uM]
UGT1A9 378	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 37400 uM]
UGT2B7 387	substrate 3264 Sources: https://molpharm.aspetjournals.org/content/67/3/665.short Page: -	yes [Km 380 uM]
CYP2C8 670	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 4800 uM]
CYP2C19 955	substrate 3264 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 6400 uM]
P-gp 1491	substrate 3264 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes
P-gp 1491	substrate 3264 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-3-glucuronide 26
P-gp 1491	substrate 3264 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
Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine.	1978 Sep 15	100809
[Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms].	1997 Jan	10921076
Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction.	1998 Dec	10070497
Epidural analgesia in children with cerebral palsy.	1998 Dec	10051932
Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.	1999	10907730
[Transverse myelopathy as a complication following long-term intrathecal application of morphine in chronic back pain].	1999 Aug	10494374
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
[Opioid receptor knockout mice].	1999 Dec	10803207
Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.	1999 Dec	10594409
Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat.	1999 Feb 26	10096766
The effects of dopamine D2 and D3 antagonists on spontaneous motor activity and morphine-induced hyperactivity in male mice.	1999 Mar	10227083
Intra-articular morphine for pain relief after knee arthroscopy.	1999 Mar	10081529
The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.	1999 May	10390729
Controlling myoclonus after high-dosage morphine infusions.	1999 May 15	10365727
Sleep impairments in rats implanted with morphine pellets.	1999 Nov	10559705
Patient-controlled analgesia with morphine plus lysine acetyl salicylate.	1999 Oct	10512278
A comparison of continuous epidural infusion and intermittent intravenous bolus doses of morphine in children undergoing selective dorsal rhizotomy.	1999 Sep-Oct	10499756
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
Intrathecal morphine suppresses NK cell activity following abdominal surgery.	2000 Apr	10764172
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
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
Prenatal morphine exposure enhances seizure susceptibility but suppresses long-term potentiation in the limbic system of adult male rats.	2000 Jun 30	10865073
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
Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects.	2000 Sep	10960384
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
Circuitry underlying antiopioid actions of cholecystokinin within the rostral ventromedial medulla.	2001 Jan	11152727
Early serial EEG in hypoxic ischaemic encephalopathy.	2001 Jan	11137658
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
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
Bupivacaine wound instillation via an electronic patient-controlled analgesia device and a double-catheter system does not decrease postoperative pain or opioid requirements after major abdominal surgery.	2001 Jan	11133625
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
Morphine with or without a local anaesthetic for postoperative intrathecal pain treatment after selective dorsal rhizotomy in children.	2001 Jan	11123736
Numerical density of mu opioid receptor expressing neurons in the frontal cortex of drug related fatalities.	2001 Jan 15	11074177

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

Name

Type

Language

MORPHINE

Common Name

English

NEPENTHE

Common Name

English

CODEINE PHOSPHATE SESQUIHYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

CODEINE MONOHYDRATE IMPURITY B [EP IMPURITY]

Common Name

English

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

Common Name

English

MORPHIUM

Common Name

English

MORPHINE [MART.]

Common Name

English

DIHYDROCODEINE HYDROGEN TARTRATE IMPURITY B [EP IMPURITY]

Common Name

English

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

Common Name

English

MORPHINE [VANDF]

Common Name

English

MORPHIA

Common Name

English

DUROMORPH

Common Name

English

ANHYDROUS MORPHINE

Common Name

English

MORPHINE [HSDB]

Common Name

English

MORPHINE EXTENDED RELEASE

Common Name

English

OSPALIVINA

Common Name

English

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

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

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