Morphine is presently the standard analgesic by which all the others are compared, and whose alternative methods of synthesis are still being developed [3-6]. Nevertheless, synthesis of morphine is not economically practical, since it is much cheaper to obtain from natural resources.
Morphine is the primary representative and primary prototype of the group of strong opioid analgesics. The most important use of morphine is its ability to eliminate pain. It is used in surgery and as a preanesthetic medication for surgical interventions before the general anesthesia procedure begins. It is widely used in myocardial infarction not only to relieve pain, but also for calming the patient and even for reducing the need of oxygen. It is used in pulmonary edema and in a few forms of diarrhea. Morphine is prescribed in all cases when NSAID action is not sufficient and requires the use of strong opioid analgesics.
Relatively simple modifications of morphine molecules lead to the formation of a number of compounds that differ in their analgesic activity.
Codeine: Codeine, 4,5-epoxy-17-methylmorphin-7-ene-3-methoxy-6-ol (3.1.20), is an elemental part of opium poppy alkaloids. Codeine differs from morphine in that hydroxyl group on C3 of the aromatic ring is methylated. The content of codeine in opium does not satisfy medicinal requirements and therefore codeine is made in a semisynthetic manner from morphine by selective methylation of the aromatic hydroxyl group on C3. The usual methylating agents result in the methylation of both hydroxyl groups. Selective methyla-tion of the hydroxyl group at C3 of the aromatic ring can be accomplished using dia-zomethane, nitrosomethylurethane, or nitrosomethylurea. However, use of these reagents presents certain difficulties in completing the reaction in large industrial scale. It was suggested that trimethylphenylammonium chloride or dimethylaniline methyltoluenesul-fonate in the presence of sodium alkoxides could be used as methylating agents. Codeine is basically synthesized by methylation of the 3-hydroxy group of the morphine ring by trimethylphenylammonium ethoxide [7,8].
Codeine is similar to morphine in terms of properties, but its pain-relieving ability is significantly less and it causes addiction to some degree. This drug is very effective in oral use and is used for average to moderate pain. It is often used as an antitussive drug. Synonyms for codeine are codyl, acutus, and others.
Heroin: Heroin, 3-diacetyl-4,5-epoxy-17-methylmorphin-7-ene (3.1.21), is synthesized by the simultaneous acetylation of the two hydroxyl groups of morphine with acetic anhydride or acetyl chloride [9,10].
Owing to its high solubility in lipids (compared to morphine), heroin quickly passes through the blood-brain barrier; however, it acts like morphine, into which it is transformed in the brain. Narcotic effects, respiratory depression, toxicity, narrow range of therapeutic action, and high danger of addiction make it less advantageous than morphine. Heroin use is prohibited in medicine, since it does not have any therapeutic value which cannot be found in other drugs.
Hydromorphone: Hydromorphone, 4,5-epoxy-3-hydroxy-N-methyl-6-oxomorphinane (3.1.22), is a compound related to morphine that differs in the absence of a double bond between C7-C8 and the presence of a keto group instead of a hydroxyl group on C6. The drug is synthesized by the isomerization of morphine in the presence of a palladium or platinum catalyst [11,12]. The other way is by oxidation of dihydroporphine [13,14].
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