Dihydrocodeine

dihydrocodeine is a semi-synthetic morphinan opioid analgesic prescribed for pain, or as an antitussive (either alone or compounded with paracetamol or aspirin). it was developed in germany in 1908 and first marketed in 1911.

dihydrocodeine is also known as drocode, paracodeine and parzone. its many brand names include synalgos dc, panlor dc, panlor ss, contugesic, new bron solution-ace, huscode, drocode, paracodin, codidol, dehace, didor continus, dicogesic, codhydrine, dekacodin, dhc, dh-codeine, didrate, dihydrin, hydrocodin, makatussin, nadeine, novicodin, rapacodin, fortuss, paramol, remedeine, dico and df-118.

dihydrocodeine is available as tablets, solutions, elixirs, and other oral forms. in some countries, the drug is available as an injectable solution for deep subcutaneous and intra-muscular administration. as with codeine, intravenous administration should be avoided as it could result in anaphylaxis and dangerous pulmonary edema. dihydrocodeine is available in suppository form on prescription.

dihydrocodeine is used as an alternative or adjunct to codeine and is similar in chemical structure. depending on individual metabolism, dihydrocodeine is 100 to 150 percent as strong as codeine.

chemistry

dihydrocodeine, or 4,5-alpha-epoxy-3-methoxy-17-methylmorphinan-6-ol, is an opioid of the morphinan class. dihydrocodeine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called a phenanthrene. a fourth nitrogen containing ring is fused to the phenanthrene at r₉ and r₁₃ with the nitrogen member looking at r₁₇ of the combined structure. this structure is called morphinan.

dihydrocodeine, along with other morphinans, contains an ether bridge between two of its rings, connecting r₄ and r₅ through an oxygen group. it also contains a hydroxy group (oh-) bound at r₆ and a methyl group located on the nitrogen atom at r₁₇. on the same ring containing the hydroxy group, codeine contains a double bond, which dihydrocodeine lacks. this results in a much more stable chemical structure and also affects its metabolism.

dihydrocodeine can be synthesized from morphine by reduction of the 7,8-double bond. it readily converts to dihydromorphine with high yields (>95%) which can be methylated to create dihydrocodeine. dihydrocodeine is analogous to the other morphinans including codeine, heroin, ethylmorphine, hydrocodone, and oxycodone.

pharmacology

dihydrocodeine exerts its effects by binding to and activating the μ-opioid receptor. this occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. the way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. this is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. they can be released in response to pain, strenuous exercise, orgasm, or general excitement.

dihydrocodeine is metabolized via cyp2d6 to the active metabolite dihydromorphine, which has a potency similar to morphine. other weakly active metabolites include nordihydrocodeine (which is formed via cyp3a4) and dihydrocodeine-6-glucuronide. although dihydrocodeine does have extremely active metabolites in the form of dihydromorphine and dihydromorphine-6-glucuronide, these metabolites are produced in such a small amount that they do not have clinically important effects.

binding affinities (k_i)

dihydrocodeine itself is a weak ligand for the opioid receptors however its main active metabolite – dihydromorphine and one of its metabolites – dihydromorphine-6-o-glucuronide show much stronger agonistic effects.