Codeine oxidative metabolism

Perpherazine and over-the-counter (OTC) ingredients codeine and dextromethorphan are made active by the debrisoquine-sparteine oxidative pathway. The percentage of an ethnic or racial population poorly metabolizing by this pathway varies greatly for example Switzerland 9-10%, Hungary 10%, United States 7%, Nigeria 3-8% and Japan 0.5% (Wood and Zhou, 1991), but if not will gain no pain relief. 

Liras 3 used an OV-17 column for Investigations on the metabolism of morphine and codeine by Arthrobacter species, and gave the gas chromatographic parameters of eight oxidized compounds, found as metabolites (14-hydroxymorphine, 14-hydroxymorphinone, 14-hydroxydihydro-morphinone, dihydromorphinone, codeinone, 14-hydroxycodeine, 14-hydroxycodeionone and 14-hydroxydihydrocodeinone). 

Chemical studies on drug metabolism. Part 1. Stereospecific synthesis of codeine 7,8-oxide and codeinone 7,8-oxide... 

Perpherazine and over-the-counter (OTC) ingredients codeine and dextromethorphan are metabolized by the debrisoquine-sparteine oxidative... 

Cell-free extracts of the whole plant were shown to be able to convert (/, 5)-reticuline to salutaridine 466). The enzymatic conversion of codeine to morphine in isolated poppy capsules was reported by Hsu et al. 467). In addition, cultures of cells in an embryogenic state were able to convert codeine to morphine at a low rate, although the major metabolic products of codeine were iV-oxides. (450). 

Tables 18.1,18.2, and 18.3 hst concentration measurements madeatdiEferenttimes during regular classes, final exams, and the summer when few students were present, respectively. A -Tetrahydrocannabinol (THC) is the major psychoactive compound in marijuana. THC is rapidly oxidized to 11-hydroxy THC and then to ll-nor-9-carboxy-A -THC, which is the main metabolite excreted. The main metabolic route of cocaine involves the hydrolysis of ester linkages to produce benzoylecgonine (BE). 6-Acetylmorphine is the main specific metabolite of heroin (3,6-diacetylmorphine). Codeine is O3 -methylmorphine. Morphine-3 p-glucuronide is a metabolite formed in vivo by the attachment of a sngar to the O3 oxygen, which facilitates elimination of morphine from the body. All three of these morphine-based derivatives are narcotics. 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-metltylenedioxy-amphetamine (MDA) are amphetamine derivatives that are commonly referred to as ecstasy.

The recent finding of N-oxides of thebaine, a relatively minor alkaloid, codeine and morphine (Figure 6-28) by Phillipson et al. (1976) in P. bracteatum and P. somniferum (Halle strain) permits the speculation that they might be involved in active metabolism. Phillipson et al, found low yields of the three alkaloid N-oxides and suggested that they do not accumulate but are either transformed into other metabolites or returned to the corresponding bases. P. somniferum seeds contain bound forms of alkaloids (Sec. 6.9.2) which on hydrolysis yields tertiary bases (Fairbairn and El-Masry, 1968) and their finding of N-oxides offers one of the best plausible explanations at this time. 

Coutts IGC, Hamblin MR, Tinley EJ (1979) The enzymatic oxidation of phenolic tetrahydroiso-quinoline-1-carboxylic acids. J Chem Soc Perkin Trans 1 2744-2750 Davis VE, Cashaw JL, McMurtrey KD, Ruchirawat S, Nimit Y (1982) Metabolism of tetrahydro-isoquinolines and related alkaloids. In Bloom F, Barchas J, Sandler M, Usdin E (eds) Beta-carbolines and tetrahydroisoquinolines. Liss, New York, p 99 Furuya T, Nakano M, Yoshikawa T (1978) Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum. Phytochemistry 17 891-893 Gates M (1953) Conversion of codeinone to codeine. J Am Chem Soc 75 4340-4341 Graves JMH, Smith WK (1967) Transformation of pregnenolone and progesterone by cultured plant cells. Nature (London) 214 124 8-1249... 

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