Morphine dependence

Morphine has a strong analgesic effect and has been used for the alleviation of postoperative and cancer pain since antiquity, but its use is now restricted because of its drug dependency. Morphine and its homologues were called opiates after opium, which was extracted from poppy seeds. This class of drugs are now termed opioids. 

Pure agonists Dextromoramide, Diamorphine (Heroin), Dipipanone, Hydrocodone, Hydromorphone, Methadone (also used for opioid dependence). Morphine, Oxycodone, Oxymorphone, Papaveretum, Pethidine (Meperidine), Tramadol... 

One of the first examples of concurrent oxidation and reduction reactions in a three-enzyme system was reported in 1996 for the biotransformation of morphine to hydromorphone (Scheme 11.2) [6]. Specifically, the NADPH-dependent morphine-6-dehydrogenase (MDH) was coupled to the NADH-dependent morphinone reductase (MR) through the action of a cofactor aspecific (accepting both NADH and NADPH) glutamate dehydrogenase. The latter cofactor regeneration reaction not only allows the use of catalytic amounts of the cofactor but also avoids the accumulation of the reduced cofactor (NADPH) produced by morphine dehydrogenase and the consequent further reduction of hydromorphone to... 

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

Note The color development depends on the temperature and duration of heating [1]. The detection limit for sterols and morphine alkaloids is in the lower nanogram range [1,2]. 

Bohn LM, Gainetdinov RR, Lin FT et al (2000) p-Opioid receptor desensitization by (3-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720-723... 

The major use of the narcotic analgesic is to relieve or manage moderate to severe acute and chronic pain. The ability of a narcotic analgesic to relieve pain depends on several factors, such as the drug, the dose, the route of administration, the type of pain, the patient, and the length of time the drug has been administered. Morphine is the most widely used opioid and an effective drug for... 

In the mid-nineteenth century, it was the custom for doctors to frequently prescribe morphine (first isolated from opium by Friedrich Serturner in 1806) and other opium preparations. Morphine did not have a major impact on medical practice until the invention of the hypodermic needle in 1840. Soldiers illness was recognized after the Civil War when more than 50,000 veterans became dependent on morphine as a result of treatment for combat injuries (Musto 1987). The public also had ready access to opium and purified drugs in grocery stores and pharmacies. Medicinal mixtures and nostrums, usually unlabelled as to contents, often contained opium or morphine. By the end of the century, many physicians had come to recognize that chronic use of morphine was a disorder (morphinism), although others in society... 

Administration of sufficient doses of an opioid antagonist after only a single therapeutic dose of morphine results in withdrawal phenomena (Bickel et al. 1987 Heishman et al. 1989 Jones 1979). Some degree of physical dependence... 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

Heishman SJ, Stitzer ML, Bigelow GE, et al Acute opioid physical dependence in postaddict humans naloxone dose effects after brief morphine exposure. J Pharmacol Exp Ther 248 127-134, 1989... 

Jones RT Dependence in non-addict humans after a single dose of morphine, in Endogenous and exogenous opiate agonists and antagonists. Edited by Way EL. New York, Pergamon, 1979, pp 557-560... 

Kleber HD, Weissman MM, Rounsaville BJ, et al Imipramine as treatment for depression in addicts. Arch Gen Psychiatry 40 649-633, 1983 Kleber HD, Riordan CE, Rounsaville BJ, et al Clonidine in outpatient detoxification from methadone maintenance. Arch Gen Psychiatry 42 391-394, 1983 Kleber HD, Topazian M, Gaspari J, et al Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. Am J Drug Alcohol Abuse 13 1-17, 1987 Kornetsky C. Brain stimulation reward, morphine-induced stereotypy, and sensitization implications for abuse. Neurosci Biobehav Rev 27 777-786, 2004 Kosten TR, Kleber HD Buprenorphine detoxification from opioid dependence a pilot study. Life Sci 42 633-641, 1988... 

Lichtman AH, Sheikh SM, Loh HH, et al Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298 1007—1014, 2001... 

Nelson CJ, Carrigan KA, Lysle DT (2000) Naltrexone administration attenuates surgery-induced immune alterations in rats. J Surg Res 94(2) 172-177 Noel RJ Jr, Kumar A (2006) Virus replication and disease progression inversely correlate with SIV tat evolution in morphine-dependent and SIV/SHIV-infected Indian rhesus macaques. Virology 346(1) 127-138... 

Noel RJ Jr, Marrero-Otero Z, Kumar R, Chompre-Gonzalez GS, Verma AS, Kumar A (2006) Correlation between SIV Tat evolution and AIDS progression in cerebrospinal fluid of morphine-dependent and control macaques infected with SIV and SHIV. Virology 349(2) 440-452 Olah ME, Caldwell CC (2003) Adenosine receptors and mammalian toll-like receptors synergism in macrophages. Mol Interv 3(7) 370-374... 

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