General
Preferred name
codeine
Synonyms
CODEINE PHOSPHATE HYDRATE ()
Codeine Phosphate ()
CODEINE ANHYDROUS ()
CODEINE PHOSPHATE ()
CODEINE SULFATE ()
IDS-NC-005(SECT.-2) ()
Codeine monohydrate ()
Codeinum monohydricum ()
Codeinum ()
Dea no. 9050 ()
Codeine ()
Codeine phosphate hemihydrate ()
Methylmorphine ()
Codeine phosphate bp ()
Galcodine ()
Codeini phosphas ()
Bepro ()
Colrex Compound ()
Codeine phosphate hydrate ()
Codeine phosphate cii ()
Codeine phosphate anhydrous ()
Ambenyl Cough Syrup ()
Evacode ()
Codeine sulfate cii ()
Codeine sulfate trihydrate ()
Codeine sulphate ()
Codeine sulfate anhydrous ()
Codeine-d3 (CRM) ()
Codeine (phosphate hydrate) ()
P&D ID
PD010106
CAS
76-57-3
70420-71-2
41444-62-6
Tags
natural product
drug
available
Approved by
FDA
First approval
1952
2009
Drug Status
illicit
approved
Drug indication
Analgesic (narcotic)
Pain
Antitussive,Antitussive,Antitussive
Cough
Antitussive
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS **General effects** Codeine is a weak narcotic pain reliever and cough suppressant that is similar to morphine and hydrocodone. A small amount of ingested codeine is converted to morphine in the body. Codeine increases tolerance to pain, reducing existing discomfort. In addition to decreasing pain, codeine also causes sedation, drowsiness, and respiratory depression [A175096]. **Antitussive activity** This drug has shown antitussive activity in clinical trials [A175102] and has been effective in cough secondary to tuberculosis and insomnia due to coughing [A175096]. Codeine suppresses the cough reflex through a direct effect on the cough center in the medulla [F3658]. **Effects on intestinal motility** Codeine may reduce intestinal motility through both a local and possibly central mechanism of action [F3661]. This may possibly lead to constipation [F3658]. The chronic use of opioids, including codeine sulfate, may lead to obstructive bowel disease, particularly in patients with underlying disorders of intestinal motility [FDA label]. **Effects on the central nervous system** Codeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic. Its primary site of action is at the _mu_ opioid receptors distributed throughout the central nervous system. The sedative activities of codeine are less potent than those of morphine [F3658]. Codeine may cause respiratory system depression by the activation of μ-opioid receptors at specific sites in the central nervous system [A175108]. **Effects on blood pressure** This drug poses an increased risk of compromised ability to maintain blood pressure due to peripheral vasodilation and other mechanisms [FDA label]. **Effects on chronic cancer pain and other types of pain** Codeine is an opioid analgesic with similar indications to those of morphine, however, is much less potent in its pain alleviating properties. Its primary action takes place at the mu opioid receptors, which are distributed throughout the central nervous system. The average duration of action is about 4 hours [F3658]. Regular dosing of opioid analgesics such as codeine in patients with severe cancer pain has been well documented to improve symptoms [A175096], [A175105].
HALF-LIFE Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours [FDA label].
MOA Codeine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug. Codeine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system [FDA label], [A175096]. The analgesic properties of codeine are thought to arise from its conversion to [Morphine], although the exact mechanism of analgesic action is unknown at this time [FDA label], [F3658].
INDICATION Codeine sulfate is a form of this drug that is commonly used. It is available in tablet form [FDA label] and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate [FDA label]. The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above [L5521], [L5524].
ROE About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine [FDA label]. The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine [F3658].
METABOLISM Approximately 70 to 80% of the ingested dose of codeine is metabolized in the liver by conjugation with glucuronic acid to _codeine-6­ glucuronide_ (C6G) and by O-demethylation to _morphine_ (about 5-10%) and N-demethylation to _norcodeine_ (about 10%) respectively. UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major metabolic enzymes mediating the glucurodination of codeine to the metabolite, _codeine 6 glucuronide_. Cytochrome P450 2D6 is the major enzyme responsible for the transformation of codeine to morphine and P450 3A4 is the main enzyme mediating the conversion of codeine to _norcodeine_. Morphine and norcodeine are then further metabolized by conjugation with glucuronic acid. The glucuronide metabolites of morphine are _morphine-3-glucuronide_ (M3G) and_ morphine-6-glucuronide _(M6G). Morphine and M6G have been proven to have analgesic activity in humans. The analgesic activity of C6G in humans is not known at this time. Norcodeine and M3G are generally not considered to have analgesic properties [FDA label].
ABSORPTION **Absorption** Codeine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration [FDA label]. **Food Effects** When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine [FDA label]. **Steady-state concentration** The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours [FDA label].
PHARMACODYNAMICS **General effects**; ; Codeine is a weak narcotic pain reliever and cough suppressant that is similar to morphine and hydrocodone. A small amount of ingested codeine is converted to morphine in the body. Codeine increases tolerance to pain, reducing existing discomfort. In addition to decreasing pain, codeine also causes sedation, drowsiness, and respiratory depression [A175096]. ; ; ; **Antitussive activity**; ; This drug has shown antitussive activity in clinical trials [A175102] and has been effective in cough secondary to tuberculosis and insomnia due to coughing [A175096]. Codeine suppresses the cough reflex through a direct effect on the cough center in the medulla [F3658].; ; **Effects on intestinal motility**; ; Codeine may reduce intestinal motility through both a local and possibly central mechanism of action [F3661]. This may possibly lead to constipation [F3658]. The chronic use of opioids, including codeine sulfate, may lead to obstructive bowel disease, particularly in patients with underlying disorders of intestinal motility [FDA label]. ; ; **Effects on the central nervous system**; ; Codeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic. Its primary site of action is at the _mu_ opioid receptors distributed throughout the central nervous system. The sedative activities of codeine are less potent than those of morphine [F3658]. Codeine may cause respiratory system depression by the activation of μ-opioid receptors at specific sites in the central nervous system [A175108].; ; **Effects on blood pressure**; ; This drug poses an increased risk of compromised ability to maintain blood pressure due to peripheral vasodilation and other mechanisms [FDA label]. ; ; ; **Effects on chronic cancer pain and other types of pain**; ; Codeine is an opioid analgesic with similar indications to those of morphine, however, is much less potent in its pain alleviating properties. Its primary action takes place at the mu opioid receptors, which are distributed throughout the central nervous system. The average duration of action is about 4 hours [F3658].; ; Regular dosing of opioid analgesics such as codeine in patients with severe cancer pain has been well documented to improve symptoms [A175096], [A175105].
INDICATION Codeine sulfate is a form of this drug that is commonly used. It is available in tablet form [FDA label] and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate [FDA label]. ; ; The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above [L5521], [L5524].
TOXICITY **Oral LD50**: 427 mg kg-1 (rat) [MSDS]. ; ; **Overdose/toxicity**; ; Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal [L5506], [FDA label]. ; ; **Teratogenic effects**; ; This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Codeine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus [FDA label]. ; ; Codeine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose [FDA label]. Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison [FDA label]. ; ; ; **Nonteratogenic effects**; ; Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment [FDA label]. ; ; Codeine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day [FDA label]. ; ; ; **The use in breastfeeding/nursing**; ; Codeine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants [FDA label].
METABOLISM Approximately 70 to 80% of the ingested dose of codeine is metabolized in the liver by conjugation with glucuronic acid to _codeine-6­ glucuronide_ (C6G) and by O-demethylation to _morphine_ (about 5-10%) and N-demethylation to _norcodeine_ (about 10%) respectively. UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major metabolic enzymes mediating the glucurodination of codeine to the metabolite, _codeine 6 glucuronide_. ; ; Cytochrome P450 2D6 is the major enzyme responsible for the transformation of codeine to morphine and P450 3A4 is the main enzyme mediating the conversion of codeine to _norcodeine_. Morphine and norcodeine are then further metabolized by conjugation with glucuronic acid. The glucuronide metabolites of morphine are _morphine-3-glucuronide_ (M3G) and_ morphine-6-glucuronide _(M6G). Morphine and M6G have been proven to have analgesic activity in humans. The analgesic activity of C6G in humans is not known at this time. Norcodeine and M3G are generally not considered to have analgesic properties [FDA label].
ABSORPTION **Absorption**; ; Codeine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration [FDA label]. ; ; **Food Effects**; ; When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine [FDA label].; ; **Steady-state concentration**; ; The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours [FDA label]. ;
DESCRIPTION Codeine is an opioid analgesic related to, but less potent than .
Marketed formulations may contain codeine sulfate (PubChem CID 6098421). (GtoPdb)
TOXICITY **Oral LD50**: 427 mg kg-1 (rat) [MSDS]. **Overdose/toxicity** Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal [L5506], [FDA label]. **Teratogenic effects** This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Codeine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus [FDA label]. Codeine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose [FDA label]. Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison [FDA label]. **Nonteratogenic effects** Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment [FDA label]. Codeine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day [FDA label]. **The use in breastfeeding/nursing** Codeine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants [FDA label].
ROE About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine [FDA label]. ; ; The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine [F3658]. ;
Cell lines
0
Organisms
1
Compound Sets
17
Cayman Chemical Bioactives
18052
15459
26514
ChEMBL Approved Drugs
CHEMBL485
CHEMBL1201099
CHEMBL4297091
ChEMBL Drugs
CHEMBL485
CHEMBL1201099
CHEMBL4297091
Concise Guide to Pharmacology 2017/18
1673
Concise Guide to Pharmacology 2021/22
1673
Concise Guide to Pharmacology 2023/24
1673
DrugBank
DB00318
DrugBank Approved Drugs
DB00318
DrugCentral
725
DrugCentral Approved Drugs
725
DrugMAP
DMJX6ZG
DrugMAP Approved Drugs
DMJX6ZG
Guide to Pharmacology
1673
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL485
NCATS Inxight Approved Drugs
UX6OWY2V7J
Other bioactive compounds
ReFrame library
External IDs
69
Properties
(calculated by RDKit )
Molecular Weight
299.15
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
1
Rotatable Bonds
1
Ring Count
5
Aromatic Ring Count
1
cLogP
1.5
TPSA
41.93
Fraction CSP3
0.56
Chiral centers
5.0
Largest ring
6.0
QED
0.8
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Class
Analgesics
Source data