Structure of codeine and morphine relationship

Morphine & Heroin

structure of codeine and morphine relationship

Codeine has been used in the past as the starting In general, the various classes of morphine derivatives Drugs bearing resemblance to codeine in effects due to close structural relationship are. Pethidine - the parts of the molecule resembling the morphine structure are one of the -OH groups with a methoxy group, morphine is converted into codeine, . The active opiates that are found in the opium poppy are morphine, codeine, thebaine, and papaverine. Oxycodone and hydrocodone are.

In general, the various classes of morphine derivatives such as ketones, semisynthetics like dihydromorphinehalogeno-morphides, esters, ethers, and others have codeine, dihydrocodeine, and isocodeine analogues. As an analgesic, codeine compares weakly to other opiates. Related to codeine in other ways are codoximethebaconcodeine-N-oxide genocodeinerelated to the nitrogen morphine derivatives as is codeine methobromide, and heterocodeinewhich is a drug six times stronger than morphine and 72 times stronger than codeine due to a small re-arrangement of the molecule, viz.

Drugs bearing resemblance to codeine in effects due to close structural relationship are variations on the methyl groups at the 3 position including ethylmorphine a. While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure. Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well.

structure of codeine and morphine relationship

History[ edit ] Codeine, or 3-methylmorphine, is an alkaloid found in the opium poppyPapaver somniferum var. Opium poppy has been cultivated and utilized throughout human history for a variety of medicinal analgesic, anti-tussive and anti-diarrheal and hypnotic properties linked to the diversity of its active components, which include morphine, codeine and papaverine.

Until the beginning of the 19th century, raw opium was used in diverse preparations known as laudanum see Thomas de Quincey 's Confessions of an English Opium-Eaterand paregoric elixirsa number of which were popular in England since the beginning of the 18th century; the original preparation seems to have been elaborated in Leidenthe Netherlands around by a chemist named Lemort; in the London Pharmacopoeia mentions an Elixir Asthmaticum, replaced by the term Elixir Paregoricum "pain soother" in The progressive isolation of opium's several active components opened the path to improved selectivity and safety of the opiates-based pharmacopeia.

Morphine Structure Activity Relationship

Codeine is the most widely used opiate in the world, [43] [44] and is one of the most commonly used drugs overall according to numerous reports by organizations including the World Health Organization and its League of Nations predecessor agency. It is one of the most effective orally administered opioid analgesics and has a wide safety margin. While codeine can be directly extracted from opium, its original source, most codeine is synthesized from the much more abundant morphine through the process of O- methylation[44] [45] through a process first completed in the late 20th century by Robert C.

Corcoran and Junning Ma. They quickly succeeded using petroleum or coal tar and a process developed at the United States' National Institutes of Health. Numerous codeine salts have been prepared since the drug was discovered.

The most commonly used are the hydrochloride freebase conversion ratio 0. The latter was introduced as Codeonal inindicated for pain with nervousness.


Codeine hydrochloride is more common worldwide and the citrate, hydroiodide, hydrobromide, tartrate, and other salts are also seen.

Brand named as Phenergan with Codeine or in generic form as promethazine with codeine. In the s it started to be mixed with soft drinks to be used as a recreational drug and was called 'syrup', 'lean', or ' purple drank '.

Drug abuse screening programs generally test urinehairsweat or saliva. Many commercial opiate screening tests directed at morphine cross-react appreciably with codeine and its metabolites, but chromatographic techniques can easily distinguish codeine from other opiates and opioids. It is important to note that codeine usage results in significant amounts of morphine as an excretion product.

Furthermore, heroin contains codeine or acetyl codeine as an impurity and its use will result in excretion of small amounts of codeine.

Poppy seed foods represent yet another source of low levels of codeine in one's biofluids.

structure of codeine and morphine relationship

Australia[ edit ] In Australia, Since February 1,preparations containing codeine are not available without a prescription. Schedule 8 preparations are subject to the strictest regulation of all medications available to consumers.

A similar tablet called "A. Both tablets are kept behind the counter and must be dispensed by a pharmacist who may limit quantities. Names of many codeine and dihydrocodeine products in Canada tend to follow the narcotic content number system Tylenol With Codeine No.

Codeine became a prescription-only medication in the province of Manitoba on February 1, It is a Schedule II controlled substance for pain-relief products containing codeine alone or more than 90 mg per dosage unit.

Preparations for cough or diarrhea containing small amounts of codeine in combination with two or more other active ingredients are Schedule V in the US, and may be dispensed in amounts up to 4 fl.

  • Codeine Molecule

In locales where dilute codeine preparations are non-prescription, anywhere from very few to perhaps a moderate percentage of pharmacists will sell these preparations without a prescription. However, many states have their own laws that do require a prescription for Schedule V drugs. Codeine is also available outside the United States as an over-the-counter drug in liquid cough-relief formulations. It is less potent than morphine and has a correspondingly lower dependence-liability than morphine.

However, the withdrawal symptoms are relatively mild and as a consequence codeine is considerably less addictive than the other opiates.

The Codeine Molecule

When analgesia beyond this is required, stronger opioids such as hydrocodone or oxycodone are favored. Because codeine needs to be metabolized to an active form, there is a ceiling effect around mg. This low ceiling further contributes to codeine being less addictive than the other opiates. The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P enzyme CYP2D6.

Some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most well-known of these are the selective serotonin reuptake inhibitors, such as fluoxetine Prozac and citalopram Celexa. Other drugs, such as rifampicin and dexamethasone, induce expression of CYP isozymes and thus increase the rate of metabolism.

It is important to note that whereas usually a CYP2D6 extensive metaboliser EM will need a higher dose of 2D6-metabolized drug for a sufficient therapeutic effect and a poor metaboliser PM may suffer from drug toxicity due to excessive plasma concentration, with the pro-drug Codeine, the opposite is true. Thus, an EM may have an adverse toxicity effect and a PM may have little or no pain relief. Pharmacology Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6.

Because of the wide variability in CYP2D6 activity among humans, the effect of codeine can vary between individuals. In persons with little or no CYP2D6 function, codeine has little or no effect.

structure of codeine and morphine relationship

Adverse effects Common adverse drug reactions associated with the use of codeine include euphoria, itching, nausea, vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention and constipation.

The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. A potentially serious adverse drug reaction, as with other opioids, is respiratory depression.

structure of codeine and morphine relationship

This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose. Another side effect commonly noticed is the lack of sexual drive and increased complications in erectile dysfunction. Some people may also have an allergic reaction to codeine, which may cause severe allergic reactions such as the swelling of skin and rashes.

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