Summary
The activity of detoxication with the cytochrome P450 family of enzymes was studied in patients with amyotrophic lateral sclerosis (ALS). The metabolic ratio (MR) of sparteine sulphate was measured, and the population of phenotypes for sparteine nitro (N)-oxidation was determined in 30 patients with ALS and 41 controls for the assay of the sparteine N-oxidation by the cytochrome P450 enzymes. A lower MR and higher frequency of efficient metabolizers were observed in the ALS group, suggesting that there is efficient sparteine N-oxidation by cytochrome P450 pathways in ALS. This tendency was more marked in 15 patients with ALS aged under 60 years.
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Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR (1984) Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature 312:169–170
Barbeau A, Clouthier T, Roy M, Plasse L, Paris S, Poirier J (1985) Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine. Lancet II:1213–1216
Eichelbaum M (1982) Defective oxidation of drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet 7:1–22
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16:183–187
Eichelbaum M, Bertilsson L, Sawe J, Zekorn C (1982) Polymorphic oxidation of sparteine and debrisoquine: related pharmacogenetic entities. Clin Pharmacol Ther 31:184–186
Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ (1987) Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Pharmacol 23:482–485
Nakano Y, Hirayama K, Terao K (1987) Hepatic ultrastructural changes and liver dysfunction in amyotrophic lateral sclerosis. Arch Neurol 44:103–106
Nebert DW, Gonzalez FJ (1987) P450 genes: structure evolution and regulation. Annu Rev Biochem 56:945–993
Sipes IG, Gandolfi AJ (1988) Biotransformation of toxicants. In: Klaassen CD, Amdur MO, Doull J (eds) Toxicology, 3rd edn. Macmillan, New York
Spencer PS, Nunn PB, Hugon J, Ludolph AC, Ross SM, Roy DN, Robertson RC (1987) Guam amyotrophic lateral sclerosis-parkinstonism-dementia linked to a plant excitant neurotoxin. Science 237:517–522
Steventon G, Williams AC, Waring RH, Pall HS, Adams D (1988) Xenobiotic metabolism in motor neuron disease. Lancet II:644–647
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Kaneko, K., Atsumi, T. & Miyatake, T. Polymorphic sparteine metabolism and amyotrophic lateral sclerosis. J Neurol 236, 452–455 (1989). https://doi.org/10.1007/BF00328505
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DOI: https://doi.org/10.1007/BF00328505