Morphine strain differences

Guitart, Xavier, Dana Bcitner-Johnson, David W. Marby, Therese A. Kosten, and Eric J. Nestler. 1992. "Fischer and Lewis Rat Strains Differ in Basal Levels of Neurofilament Proteins and Their Regulation by Chronic Morphine in the Mesolimbic Dopamine System." Synapse 12 242-53. 

The oxidative reactions of this sequence are catalyzed by the microsomal P-450 system [69, 70, 71]. A P-450 system from rat liver can also oxidize morphine [72]. One product of this oxidation is morphinone, a highly toxic electrophile that couples with thiol groups. The latter reaction may deplete glutathione and in other ways may account for the hepatotoxicity of morphine [73, 74]. The demethylation of codeine to morphine probably accounts for the analgesic action of codeine, and people with a defect in this demethylating system probably get no analgesia from codeine [75, 76]. Rats, too, show strain differences in the ability to demethylate codeine to morphine [77]. Quinidine, quinine, or sparteine inhibit the conversion of codeine to morphine, presumably by inhibiting the P-450 enzyme [71, 78]. While O-demethylation converts codeine to morphine, N-demethylation also occurs and produces norcodeine [79]. 

K. Aghajanian, and Eric J. Nestler. 1993. "Lewis and Fischer Rat Strains Display Differences in Biochemical, Electrophysiologica), and Behavioral Parameters Studies in the Nucleus Accumbens and Locus Coeruleus of Drug Naive and Morphine-Treated Animals." Brain Research 611 7-17. 

There are ample a priori reasons to suspect that different plants of a single species may elaborate different amounts of alkaloids. It is well known that strains of tobacco and of lupines can be selected to yield greater or lesser amounts of alkaloids. That mutants occur is also highly probable. In this connection it is not unreasonable to suspect that the opium poppy may in fact be a mutant which was selected and cultivated because of its unique alkaloids. Neither morphine nor codeine have been found in any other species of Papaver and the basic ring system in these alkaloids has been found in part only in alkaloids derived from plants of a family (Menispermaceae) whose affinities with Papaveraceae can only be remote. 

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