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Published: Kem. Ind. 53 (5) (2004) 209–216
Paper reference number: KUI-43/2002
Paper type: Professional paper
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Opiod Analgesics

B. Zorc


The opiates are perhaps the oldest drugs, known to man for more than 2000 years. Opium is the sticky exudate obtained from the poppy (Papaver somniferum, Papaveracež). It containes a complex mixture of almost twenty-five alkaloids. The principle alkaloid in opium and the one responsible for analgesic activity, is morphine. For two hundred years it has been one of the most effective pain-killers available to medicine. It is specially good for treating dull, constant pain in patients with progressing carcinoma. It acts in the brain by binding at the same opiod receptors as endogenous opiod peptides. Unfortunately, it has a large number of side-effects which include the following: depression of the respiratory centre, tolerance, dependence, constipation, euphoria, sedation, nausea and pupil constriction. Tolerance and dependence are particularly dangerous and lead to severe withdrawal symptoms when the drug is no longer taken. The following strategies in the development of morphine analogues were applied: variation of substituents, drug extension, simplification and rigidification of the morphine molecule. Variation of substituents revealed that the phenolic and amino groups, the aromatic ring and correct stereochemistry are essential to the analgetic activity, while ether bridge and double bond are not essential. Masking of alcohol group led to the less polar compounds that entered easier the blood-brain barrier. Introduction of a hydroxyl group at position 14 or a phenylethyl group on nitrogen atom gave the compounds with increased activity. On the other hand, attachment of an allyl or a cyclopropylmethylene group at N-atom led to antagonists. Simplification of the morphine molecule gave a number of useful analgesic drugs: morphinans (levorphanol), benzomorphans (metazocine, phenazocine, pentazocine, bremazocine), pethidines (pethidine, ketobemidone, fentanyl, tramadol) and methadone. Rigidification of the morphine structure resulted with oripavine series (oripavine, etorphine, buprenorphine). At the moment, buprenorphine is the most successful opiate analogue where analgesia has been separated from dangerous side effects.

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opium, morphine, morphinans, benzomorphans, pethidine, methadone, opium analgesics