1.0 2009-07-21 20:26:35 UTC 2026-05-14 16:25:23 UTC T3D2749 Codeine SmallMolecule Codeine belongs to the morphinans, a class of alkaloids and derivatives within the organic compounds. It has the formula C18H21NO3, an average molecular weight of 299.36 g/mol, and exists as a solid at room temperature. This exogenous compound is an opioid analgesic, antitussive, opioid receptor agonist, and prodrug (PMC5357098, PMC6644518). It is used as a treatment for pain (PMC6205722, PMC6644518) and cough (PMC6205722). However, it is associated with lethargy and depression (PMC7012325). Codeine targets five proteins: the Mu-type opioid receptor (OPRM1), Delta-type opioid receptor (OPRD1), Kappa-type opioid receptor (OPRK1), Cytochrome P450 2D6 (CYP2D6), and the Voltage-gated inwardly rectifying potassium channel KCNH2. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex; since the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase, subsequently affecting the release of nociceptive neurotransmitter. The compound has been detected in skin and hair. Recorded exposure routes include oral, subcutaneous, intramuscular, inhalation, and touch. It is found in 27 recorded sources, including healthcare, pharmaceuticals and veterinary products (analgesics, medical devices, cough and cold preparations), drinking water and water supply, indoor air, textiles, leather and furnishings, household cleaning and consumer products, and electrical and electronic equipment. Additionally, codeine is used in Low-Density Polyethylene, High-Density Polyethylene, and Polyamide plastics. Drug Food Toxin Synthetic Toxin Organic Compound Amine Ether Drug Food Toxin Analgesic Analgesic, Opioid Narcotic Antitussive Agent Opiate Agonist Metabolite Synthetic Compound PFAS Phytotoxin (-)-Codeine (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol 3-Methylmorphin 3-methylmorphine 7,8-Didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol Actacode Bisoltus Bromophar Bronchicum Bronchodine Codant Codedrill Codein Codeína Codeine anhydrous Codeinum Codeisan Coderpina Codicalm Codicept Codinex Coducept Cougel Coutan Dinco Farmacod Galcodine L-Codeine Methylmorphine Morphine 3-methyl ether Morphine monomethyl ether morphine-3-methyl ether Norcodeine, N-Methyl Norcodine, N-Methyl O(3)-Methylmorphine O3-Methylmorphine Pectoral Tussoret C18H21NO3 299.3642 299.152143543 (1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol (1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol 76-57-3 [H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1 OROGSEYTTFOCAN-DNJOTXNNSA-N Organic compounds Alkaloids and derivatives Morphinans Morphinans Alkyl aryl ethers Anisoles Aralkylamines Azacyclic compounds Coumarans Hydrocarbon derivatives Organopnictogen compounds Oxacyclic compounds Phenanthrenes and derivatives Piperidines Secondary alcohols Tetralins Trialkylamines Alcohol Alkyl aryl ether Amine Anisole Aralkylamine Aromatic heteropolycyclic compound Azacycle Benzenoid Coumaran Ether Hydrocarbon derivative Morphinan Organic nitrogen compound Organic oxygen compound Organoheterocyclic compound Organonitrogen compound Organooxygen compound Organopnictogen compound Oxacycle Phenanthrene Piperidine Secondary alcohol Tertiary aliphatic amine Tertiary amine Tetralin Aromatic heteropolycyclic compounds Isoquinoline alkaloids morphinane alkaloid organic heteropentacyclic compound Detected and Not Quantified Exogenous Cytoplasm Extracellular Membrane Hair Skin Codeine Pathway Codeine Action Pathway SMP0000405 Codeine Metabolism Pathway SMP0000621 Codeine Opioid Action Pathway SMP0122959 Glutethimide Action Pathway SMP0126131 Codeine Drug Metabolism Action Pathway SMP0142777 Solid White powder. melting_point 157.5°C boiling_point 250°C at 2.20E+01 mm Hg solubility 9000 mg/L (at 20°C) logp 1.19 logp 1.20 ALOGPS logs -2.72 ALOGPS solubility 5.77e-01 g/l ALOGPS logp 1.34 ChemAxon pka_strongest_acidic 13.78 ChemAxon pka_strongest_basic 9.19 ChemAxon iupac (1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol ChemAxon average_mass 299.3642 ChemAxon mono_mass 299.152143543 ChemAxon smiles [H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O ChemAxon formula C18H21NO3 ChemAxon inchi InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1 ChemAxon inchikey OROGSEYTTFOCAN-DNJOTXNNSA-N ChemAxon polar_surface_area 41.93 ChemAxon refractivity 84.6 ChemAxon polarizability 31.95 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 4 ChemAxon donor_count 1 ChemAxon physiological_charge 1 ChemAxon formal_charge 0 ChemAxon Oral, Intramuscular. Well absorbed following oral administration with a bioavailability of approximately 90%. Maximum plasma concentration occurs 60 minutes post-administration. Food does not effect the rate or extent of absorption of codeine. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6 to morphine. 70-80% of the dose undergoes glucuronidation to form codeine-6-glucuronide. This process is mediated by UDP-glucuronosyltransferase UGT2B7 and UGT2B4. 5-10% of the dose undergoes O-demethylation to morphine and 10% undergoes N-demethylation to form norcodeine. CYP2D6 mediates the biotransformation to morphine. CYP3A4 is the enzymes that mediates the conversion to norcodiene. Morphine and norcodeine are further metabolized and undergo glucuronidation. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Both morphine and morphine-6-glucuronide are active and have analgesic activity. Norcodiene and M3G do not have any analgesic properties. Route of Elimination: 90% of the total dose of codeine is excreted through the kidneys, of which 10% is unchanged codeine. Half Life: Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours. No indication of carcinogenicity to humans (not listed by IARC). For treatment and management of pain (systemic). It is also used as an antidiarrheal and as a cough suppressant. #<HealthEffect::ActiveRecord_Associations_CollectionProxy:0x00007f721f7e0c00> Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue. Naloxone antagonizes most effects of codeine. Protect the airway as Naloxone may induce vomiting. Naloxone has a shorter duration of action than codeine; repeated doses may be needed. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal. (L1712) DB00318 HMDB04995 5284371 CHEMBL485 4447447 C06174 124030 608902 16714 CODEINE Codeine Codeine 15495019 11092114 15102399 8926744 10997932 12423011 10517543 10102911 9042709 11450354 10468028 10572984 8706777 3518729 10517550 16419403 10027657 10940601 8035160 10360425 6371380 9491963 10219671 Drugs.com: http://www.drugs.com/cons/Codeine.html RxList: The Internet Drug Index (2009).: http://www.rxlist.com/ BE0000420 Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. BE0000770 Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. IC50 0.105 uM BindingDB 50019351 BE0000632 Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. IC50 15 uM BindingDB 50019351 BE0002363 IC50 104 uM BindingDB 50019351 BE0000090 IC50 301.99517 uM BindingDB 50019351