General
Preferred name
MORPHINE
Synonyms
MORPHINE SULFATE HYDRATE ()
Morphine Sulfate ()
MORPHINE HYDROCHLORIDE ()
MORPHINE SULFATE ()
Morphine (anhydrous) ()
Depodur ()
Morphium ()
Anhydrous morphine ()
Morphine extended release ()
IDS-NM-009 ()
Ospalivina ()
Infumorph ()
Morphine polistirex ()
Morphia ()
Morphine anhydrous ()
Avinza ()
N02AA01 ()
Hydromorphone hydrochloride impurity, morphine- ()
Nepenthe ()
Kadian ()
Morphine ()
Astramorph Pf ()
Morphine sulfate hydrate ()
Morphine sulphate anhydrous ()
Duramorph ()
NSC-11441 ()
Morphgesic SR ()
Morphine sulphate ()
Rhotard ()
Dolcontin ()
Morphabond ()
Morphine sulphate pentahydrate ()
Srm-Rhotard ()
Astramorph ()
Moscontin ()
Sevredol ()
Morphine sulfate cii ()
Morphine sulfate pentahydrate ()
Ms Contin ()
Duramorph Pf ()
Morphabond ER ()
Filnarine SR ()
Oramorph ()
Zomorph ()
Arymo ER ()
Moraxen ()
Oramorph Sr ()
Morphini sulfas ()
Morcap ()
Morphine sulfate anhydrous ()
Mst Continus ()
Oramorph UDV ()
Duromorph ()
Arymo ()
Morcap SR ()
Kapanol ()
Morphine sulfate,anhydrous ()
Morphine sulfate (autoinjector) ()
Morphine chlorhydrate ()
(-)-morphine hydrochloride ()
Morphine hydrochloride trihydrate ()
Morphine hcl ()
Morph HCl ()
Thebametten ()
Morphini hydrochloridum ()
Vendal ()
Morphinum muriaticum ()
Epimore ()
Morphine hydrochloride hydrate ()
Morphine Hydro Chloride ()
Morphine-d3 (CRM) ()
Morphine (sulfate hydrate) ()
P&D ID
PD010118
CAS
47106-99-0
57-27-2
52-26-6
67293-88-3
6211-15-0
Tags
drug
natural product
biased GPCR ligand
available
Approved by
FDA
Drug Status
investigational
approved
Drug indication
Analgesic (narcotic)
Chronic pain
Max Phase
Phase 4
First approval
1984
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
The elimination of morphine and its metabolites is mainly done by the urine from which only 2-10% of the dose corresponds to the unchanged form.[A176059] However, right after oral administration, there is extensive presystemic elimination through the passage across the bowel wall and through the liver. From the elimination route, about 70-80% of the administered dose is excreted after 48 hours.[A176119]
PHARMACODYNAMICS
The binding of morphine in the opioid receptors blocks the transmission of nociceptive signals, it activates the signaling of pain-modulating neurons in the spinal cord and inhibits the transmission from primary afferent nociceptors to the dorsal horn sensory projection cells.[A176035] The onset of action is of 6-30 minutes.[A176035] The excess in the consumption of morphine and opioids, in general, can produce changes in the synaptic neuroplasticity mainly in the postsynaptic sites, dendritic terminals and modifications in the density.[A176056] Analysis of intravenous morphine showed that the attenuation of pain and analgesic effect was sex-dependent. The potency of the morphine effect is of around half in men when compared to the effect in women, as observed with an EC50 of 76 and 33 ng/ml respectively. As well, the effect of the active metabolite of morphine, morphine-6-glucuronide, was only about 22 times less potent than the morphine when analyzed in pupil constriction.[A176116]
MOA
It is important to consider that about 85% of the effect observed by morphine administration is due to the activity of morphine-6-glucuronide.[A176059] Morphine and its metabolites act as agonists of the mu and the kappa opioid receptors which derive later into analgesia.[A176035] The mu-opioid receptor is a key part of the effect of morphine in the ventral tegmental area which reinforces the effects of morphine. However, in studies with delta opioid receptor knock-out mice, it was reported a reduction in the rewarding effect of morphine suggesting that the rewarding effect of morphine is related to activity towards the delta opioid receptor in the nucleus accumbens.[A176050] From the three target receptors of morphine, the mu receptor is associated with the side effects of the morphine such as modifications in the respiratory system and addiction.[A176056]
INDICATION
Morphine is used for the management of chronic moderate-to-severe pain.[A176050] Opioids, including morphine, can manage pain effectively when used for a short amount of time. The use of opioids for longer periods needs to be monitored as they can develop a physical dependence, addiction disorder and drug abuse.[L5728]
TOXICITY
Based on cases of morphine intoxication, the LD50 is reported to be of 0.78 mcg/ml in males and 0.98 mcg/ml in females.[A176167] The cases of overdose are presented mainly as respiratory depression, extreme somnolence, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, miosis and mydriasis. These symptoms can lead to pulmonary edema, bradycardia, hypotension cardiac arrest and death.[FDA label] In cases of overdose, it is key to re-establish the patient airway and consider using oxygen and vasopressors to manage the circulatory shock and pulmonary edema. Consider the use of naloxone as an antidote and avoid the use of morphine antagonists if there aren't clear signs of respiratory depression and monitor the signs of withdrawal when used.[FDA label] Morphine was shown to increase the DNA fragmentation, to be mutagenic in micronucleus, and to induce chromosomal aberration. All these effects are thought to be related to the morphine-induced increase in glucocorticoid levels. Related to the effects on fertility, morphine is shown to reduce the number of total pregnancies, increase in the incidence of pseudopregnancies, reduction in the number of implantation sites and changes in the hormonal profile. On the other hand, carcinogenic studies haven't been done so far.[FDA label]
METABOLISM
Around 90% of morphine is glucuronidated and sulfated in position 3 and 6 by the activity of UDP-Glucuronosyltransferase-2B7 in the liver.[A176059] The glucuronide metabolites do not reach steady-state before 60 hours. From these metabolites, morphine-3-glucuronide presents lower clearance, a smaller volume of distribution and shorter half-life when compared to the most active biologically metabolite morphine-6-glucuronide.[A176035] Other than this major metabolites, some other metabolites are codeine, normorphine, and morphine ethereal sulfate.[A176119]
ABSORPTION
Morphine presents an almost complete absorption mainly done in an alkaline environment in the upper intestine as well as in the rectal mucosa.[A176119] Morphine presents significant first-pass metabolism and thus, oral doses are required to be six times bigger than parenteral administration in order to achieve the same analgesic effect. The steady-state concentration of morphine is achieved after 24-48 hours of initial administration,[A176035] and a peak plasma concentration of 283 nmol/L can range from 15 min when administered parentally to 90 min when administered orally.[A176122, A176164] The AUC of morphine is reported to be in the range of 225-290 nmol.h/L with a bioavailability that can range from 80-100% depending on the route of administration.[A176164]
HALF-LIFE
Morphine presents an equilibrated half-life of 2-3 hours.[A176116]
PHARMACODYNAMICS
The binding of morphine in the opioid receptors blocks the transmission of nociceptive signals, it activates the signaling of pain-modulating neurons in the spinal cord and inhibits the transmission from primary afferent nociceptors to the dorsal horn sensory projection cells.[A176035]; ; The onset of action is of 6-30 minutes.[A176035] The excess in the consumption of morphine and opioids, in general, can produce changes in the synaptic neuroplasticity mainly in the postsynaptic sites, dendritic terminals and modifications in the density.[A176056]; ; Analysis of intravenous morphine showed that the attenuation of pain and analgesic effect was sex-dependent. The potency of the morphine effect is of around half in men when compared to the effect in women, as observed with an EC50 of 76 and 33 ng/ml respectively. As well, the effect of the active metabolite of morphine, morphine-6-glucuronide, was only about 22 times less potent than the morphine when analyzed in pupil constriction.[A176116]
MOA
It is important to consider that about 85% of the effect observed by morphine administration is due to the activity of morphine-6-glucuronide.[A176059] Morphine and its metabolites act as agonists of the mu and the kappa opioid receptors which derive later into analgesia.[A176035] The mu-opioid receptor is a key part of the effect of morphine in the ventral tegmental area which reinforces the effects of morphine. However, in studies with delta opioid receptor knock-out mice, it was reported a reduction in the rewarding effect of morphine suggesting that the rewarding effect of morphine is related to activity towards the delta opioid receptor in the nucleus accumbens.[A176050]; ; From the three target receptors of morphine, the mu receptor is associated with the side effects of the morphine such as modifications in the respiratory system and addiction.[A176056]
INDICATION
Morphine is used for the management of chronic moderate-to-severe pain.[A176050]; ; Opioids, including morphine, can manage pain effectively when used for a short amount of time. The use of opioids for longer periods needs to be monitored as they can develop a physical dependence, addiction disorder and drug abuse.[L5728]
TOXICITY
Based on cases of morphine intoxication, the LD50 is reported to be of 0.78 mcg/ml in males and 0.98 mcg/ml in females.[A176167] The cases of overdose are presented mainly as respiratory depression, extreme somnolence, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, miosis and mydriasis. These symptoms can lead to pulmonary edema, bradycardia, hypotension cardiac arrest and death.[FDA label]; ; In cases of overdose, it is key to re-establish the patient airway and consider using oxygen and vasopressors to manage the circulatory shock and pulmonary edema. Consider the use of naloxone as an antidote and avoid the use of morphine antagonists if there aren't clear signs of respiratory depression and monitor the signs of withdrawal when used.[FDA label]; ; Morphine was shown to increase the DNA fragmentation, to be mutagenic in micronucleus, and to induce chromosomal aberration. All these effects are thought to be related to the morphine-induced increase in glucocorticoid levels. Related to the effects on fertility, morphine is shown to reduce the number of total pregnancies, increase in the incidence of pseudopregnancies, reduction in the number of implantation sites and changes in the hormonal profile. On the other hand, carcinogenic studies haven't been done so far.[FDA label]
DESCRIPTION
Morphine is an opiate class compound, isolated from the opium poppy (Papaver somniferum). It is a fast-acting narcotic. Morphine is used to make other opioids such as , and (heroin).
(GtoPdb)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
19
BiasDB
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NPC Screening Collection
ReFrame library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
96
Molecular Weight
285.14
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
2
Rotatable Bonds
0
Ring Count
5
Aromatic Ring Count
1
cLogP
1.2
TPSA
52.93
Fraction CSP3
0.53
Chiral centers
5.0
Largest ring
6.0
QED
0.7
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Class
Analgesics
Source data
