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

CN1CC[C@@]23[C@H]4OC5=C2C(C[C@@H]1[C@@H]3C=C[C@@H]4O)=CC=C5O

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 231 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16580639	Agonist 2752
Kappa-type opioid receptor 61 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 2752
Delta-type opioid receptor 46 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 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain severe 27 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018565s022lbl_Duramorph.pdf	Palliative		Approved 8583	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 Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/28530786/	Sources: https://pubmed.ncbi.nlm.nih.gov/28530786/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	CYP1A2 1197 CYP2C19 1119 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2E1 729 UGT2B7 456 UGT1A1 479 UGT1A3 470 UGT1A6 343 UGT1A8 323 UGT1A9 423 UGT1A10 331 OCT1 393 P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1932	inhibitor 4027 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-3-glucuronide 27
P-gp 1932	inhibitor 4027 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	no	morphine-6-glucuronide 27

Drug as victim

Target	Modality	Activity	Metabolite
CYP1A2 1197	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2A6 626	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2B6 776	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2E1 729	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 10100 uM]
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 12600 uM]
CYP3A4 1946	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 14150 uM]
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18000 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 18700 uM]
CYP2C9 1193	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 25400 uM]
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 2600 uM]
OCT1 393	substrate 4014 Sources: https://www.sciencedirect.com/science/article/pii/S0006295213003900 Page: -	yes [Km 3.4 uM]
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 3200 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12920162/ Page: -	yes [Km 37400 uM]
UGT2B7 456	substrate 4014 Sources: https://molpharm.aspetjournals.org/content/67/3/665.short Page: -	yes [Km 380 uM]
CYP2C8 810	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 4800 uM]
CYP2C19 1119	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/0049825031000121608 Page: -	yes [Km 6400 uM]
P-gp 2052	substrate 4014 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes
P-gp 2052	substrate 4014 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-3-glucuronide 27
P-gp 2052	substrate 4014 Sources: https://pubs.asahq.org/anesthesiology/article/96/4/913/39246/Interaction-of-Morphine-Fentanyl-Sufentanil Page: -	yes	morphine-6-glucuronide 27

Sourcing

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

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
Morphine inhibits human microglial cell production of, and migration towards, RANTES.	2000	11106302
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
Apnoea with intrathecal morphine.	2000 Dec	11153309
The development of pain-related behaviour and opioid tolerance after neuropathy-inducing surgery and sham surgery.	2000 Dec 1	11068110
Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction.	2000 Jul	10964147
Systemic naloxone enhances cerebral blood flow in anesthetized morphine-dependent rats.	2000 Nov 24	11090647
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
Downbeat nystagmus associated with intravenous patient-controlled administration of morphine.	2000 Sep	10960401
Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects.	2000 Sep	10960384
mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia.	2001	11077066
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
A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling.	2001 Feb 2	11067846
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
Morphine nerve paste.	2001 Jan	11147863
Prehospital management of rapid atrial fibrillation: recommendations for treatment protocols.	2001 Jan	11146008
Early serial EEG in hypoxic ischaemic encephalopathy.	2001 Jan	11137658
Randomized clinical trial of diathermy versus scalpel incision in elective midline laparotomy.	2001 Jan	11136307
Opiates, intracranial pressure, and autoregulation.	2001 Jan	11135743
Buprenorphine substitution ameliorates spontaneous withdrawal in fentanyl-dependent rat pups.	2001 Jan	11134491
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
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
A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain.	2001 Jan	11133596
Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme.	2001 Jan	11125020
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
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
Heroin-related deaths in Victoria: a review of cases for 1997 and 1998.	2001 Jan 1	11137276
Numerical density of mu opioid receptor expressing neurons in the frontal cortex of drug related fatalities.	2001 Jan 15	11074177
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
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

Name

Type

Language

MORPHINE

Common Name

English

N02AA01

Preferred 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

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-4,5?-epoxy-17-methylmorphinan-3,6?-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