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CODEINE Basic information
Product Name:CODEINE
Synonyms:CODEINE HYDROCHLORIDE-HYDRATE;CODEINE;CODEINE BASE;MORPHINAN-6-OL,7,8-DIDEHYDRO-4,5-EPOXY-3-METHOXY-17-METHYL-, (5A,6A)-;7,8-Didehydro-4,5alpha-epoxy-3-methoxy-17-methyl morphinan-6alpha-ol;7,8-didehydro-4,5-alpha-epoxy-3-methoxy-17-methyl-morphinan-6-alpha-o;7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methyl-morphinan-6alpha-o;7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-,(5alpha,6alpha)-morphinan-6-o
Product Categories:Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
Mol File:76-57-3.mol
CODEINE Structure
CODEINE Chemical Properties
Melting point 156-158?C
Boiling point 440.69°C (rough estimate)
density 1.3200
refractive index 1.5500 (estimate)
Fp 9℃
storage temp. 2-8°C
solubility Soluble in boiling water, freely soluble in ethanol (96 per cent).
pka8.21(at 25℃)
Water Solubility 47.62g/L(25 ºC)
Stability:Stable, but light sensitive. Combustible. Incompatible with strong oxidizing agents, bromides, iodides, heavy metal salts.
EPA Substance Registry SystemCodeine (76-57-3)
Safety Information
Hazard Codes F,T
Risk Statements 11-23/24/25-39/23/24/25
Safety Statements 7-16-36/37-45
RIDADR UN 1230 3/PG 2
WGK Germany 1
Hazardous Substances Data76-57-3(Hazardous Substances Data)
ToxicityLD50 oral in rat: 427mg/kg
MSDS Information
SigmaAldrich English
CODEINE Usage And Synthesis
DescriptionCodein phosphate and hydrochloride caused contact dermatitis in a worker in the production of opium alkaloids. Codeine bitartrate caused contact dermatitis in a worker in the production of concentrated poppy straw. Codeine was a sensitizer in a laboratory worker at an opiate-manufacturing pharmaceutical company, also sensitive to the baine.
Chemical PropertiesWhite Solid
Chemical PropertiesCodeine, also known as methylmorphine, C18H21NO3· H2O, is a colorless white crystalline substance, slightly soluble in water, soluble in alcohol and chloroform, effloresces slowly in dry air.
UsesCodeine is derived from opium by extraction or by the methylation of morphine. For medical use, codeine is usually offered as the dichloride, phosphate, or sulfate. Codeine is habit forming. Codeine is known to exacerbate urticaria (familiarly known as hives). Since codeine is incorporated in numerous prescription medicines for headache, heartburn, fatigue, coughing, and relief of aches and pains, persons with a history of urticaria should make this fact known to their physician. Codeine is sometimes used in cases of acute pericarditis to relieve severe chest pains in early phases of disease. Codeine is sometimes used in drug therapy of renal (kidney) diseases.
UsesCodeine is used in medicine for its narcoticanalgesic action. It is used as a sedative incough mixtures. Codeine occurs in opiumfrom 0.7% to 2.5%. It is prepared frommorphine by methylating the phenolic OHgroup of the morphine. It is also obtained byextraction of opium.
UsesPresent in opium from 0.7% to 2.5%, depending on the source. Weak narcotic analgesic, perhaps due to conversion to morphine, with minimal hypnotic properties; potent antitussive. Controlled substance (opiate)
DefinitionChEBI: A morphinane alkaloid found in the opium poppy, Papaver somniferum var. album; has analgesic, anti-tussive and anti-diarrhoeal properties.
Definitioncodeine: An alkaloid C18H21NO3found in opium. It is structurally similarto morphine, from which it isproduced, and is used in the form ofthe sulphate or phosphate as apainkiller and cough medicine.Codeine is converted into morphinein the liver. It is used to some extentas a recreational drug. In the UK it isa class B drug but can be obtained incomposite over-the-counter preparationsin which it has a low concentrationand is combined with paracetamolor ibuprofen. See also opioids.
Brand nameAlgisedal;Codol;Diarrest;Novacetol;Sedarene.
World Health Organization (WHO)Codeine, which has antitussive, opioid analgesic and antidianhoeal activity, was first extracted from opium in 1832 and has since been widely used in medicine. The development of dependence and its potential for abuse resulted in the control af the substance under Schedule II of the 1961 Single Convention on Narcotic Drugs. Preparations containing codeine remain widely available and are included in the WHO Model List of Essential Drugs.(Reference: (WHTAC1) The Use of Essential Drugs, 2nd Report of the WHO Expert Committee, 722, , 1985)
Biological FunctionsLike morphine, codeine is a naturally occurring opioid found in the poppy plant. Codeine is indicated for the treatment of mild to moderate pain and for its antitussive effects. It is widely used as an opioid antitussive because at antitussive doses it has few side effects and has excellent oral bioavailability. Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect. It is one of the most commonly used opioids in combination with nonopioids for the relief of pain. The administration of 30 mg of codeine in combination with aspirin is equivalent in analgesic effect to the administration of 65 mg of codeine. The combination of the drugs has the advantage of reducing the amount of opioid required for pain relief and abolition of the pain via two distinct mechanisms, inhibition of prostanoid synthesis and opioid inhibition of nociceptive transmission. When given alone, orally administered codeine has about one-tenth to one-fifth the potency of morphine for the relief of pain. In addition, IV codeine has a greater tendency to release histamine and produce vasodilation and hypotension than does morphine. Thus, the use of IV codeine is rare. Codeine is rarely addictive and produces little euphoria.
General DescriptionCodeine is an alkaloid that occurs naturally in opium, butthe amount present is usually too small to be of commercialimportance. Consequently, most commercial codeine is preparedfrom morphine by methylating the phenolic OHgroup. It occurs as levorotatory, colorless, efflorescent crystals,or as a white crystalline powder. It is light sensitive.Codeine is a monoacidic base and readily forms salts withacids, with the most important being the sulfate and thephosphate. The acetate and methylbromide derivatives havebeen used to a limited extent in cough preparations.The general pharmacological action of codeine is similarto that of morphine, but it does not possess the sameanalgesic potency.
General DescriptionColorless to white crystalline solid or white powder. Sublimes at 284°F. Odorless. Bitter taste. pH (saturated aqueous solution) 9.8.
Air & Water ReactionsCODEINE is light sensitive and sensitive to prolonged exposure to air. Insoluble in water.
Reactivity ProfileCODEINE is incompatible with bromides, iodides and salts of heavy metals. . CODEINE is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
HazardHabit-forming narcotic, sale legally restricted.
Health HazardThe toxic effects due to codeine are similarbut less toxic than those of morphineand other opium alkaloids. An overdosecan cause respiratory failure. It is a weakdepressant of the central nervous system.It also exhibits stimulant action. Toxicsymptoms from high dosages may includedrowsiness, sleep, tremors, excitement, andhallucinations. It may also produce gastricpains and constipation. An oral LD50 value in rats is 427 mg/kg. The habit-forming effectsof codeine are lower than those associatedwith morphine.
Nagamatsu and coworkers (1985) havereported in vitro formation of codeinonefrom codeine by rat or guinea pig liverhomogenate. Codeinone may be a metabolicintermediate in the presence of nicotinamideadenine dinucleotide (NAD). Its acute toxicityin mice was determined to be 30 timeshigher than that of codeine.
Fire HazardCODEINE is combustible.
Contact allergensCodeine has been reported as an occupational sensitizer in workers in the production of opium alkaloids. Codeine has been responsible for fixed drug eruptions or generalized dermatitis. Cross-sensitivity is expected to morphine.
Purification MethodsCodeine crystallises from water or aqueous EtOH. Dry it at 80o. Evaporation of a CHCl3 extract gives a colourless glass which crystallises on scratching. It crystallises from H2O as the monohydrate, m 157-158.5o, and has [] D -136o (c 2.8, EtOH). The hydrobromide crystallises in needles from H2O, and effervesces at 151-160o, solidifies and remelts with extensive decomposition at 273-278o. It sublimes at 100o/0.03mm. [Gates J Am Chem Soc 75 4340 1953, Dauben et al. J Org Chem 44 1567 1979, Beilstein 27 II 136, 27 III/IV 2228.]
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