Isotopic effect study of propofol deuteration on the metabolism, activity, and toxicity of the anesthetic

Journal of Medicinal Chemistry

Volumn 45, Issue 26, 2002, Pages 5806-5808

  Helfenbein, J ^a   Lartigue, C ^b   Noirault, E ^b   Azim, E ^a   Legailliard, J ^a   Galmier, M J ^a   Madelmont, J C ^b  

^a Orphachem   (France)

^b INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

DEUTERIUM; INTRAVENOUS ANESTHETIC AGENT; PROPOFOL;

ANIMAL EXPERIMENT; ARTICLE; DRUG METABOLISM; DRUG STRUCTURE; GAS CHROMATOGRAPHY; GENERAL ANESTHESIA; HUMAN; HUMAN TISSUE; INTRAVENOUS ANESTHESIA; LD 50; LIVER MICROSOME; MASS SPECTROMETRY; MOUSE; NONHUMAN; SEDATION; TOXICITY TESTING;

ANESTHETICS, INTRAVENOUS; ANIMALS; DEUTERIUM; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HUMANS; HYPNOTICS AND SEDATIVES; MICE; MICROSOMES, LIVER; PROPOFOL;

EID: 0037137591     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020864q     Document Type: Article

References (22)

1. Gepts, A.; Trenchant A, Propofol. Anaesth. Pharmacol. Rev. 1995, 3, 46-56.
2. Franks, N. P.; Lieb, W. R. Molecular and cellular mechanisms of general anesthesia. Nature 1994, 367, 607-614.
3. 14C-propofol. Xenobiotica 1988, 18, 429-440.
4. Trapani, G.; Altomare, C.; Sanna, E.; Biggio, J.; Liso, G. Propofol in anesthesia. Mechanism of action, structure-activity relationships and drug delivery. Curr. Med. Chem. 2000, 7, 249-271.
5. Guitton, J.; Buronfosse, T.; Desage, M.; Flinois, J. P.; Perdrix, J. P.; Brazier, J. L.; Beaune, P. Possible involvement of multiple human cytochrome P450 in the liver metabolism of propofol. Br. J. Anaesth. 1998, 80, 788-795.
6. Nelson, S. D.; Pohl, L. R.; Trager, W. F. Primary and β-secondary deuterium isotope effects in N-deethylation reactions. J. Med. Chem. 1975, 18, 1062-1065.
7. McMahon, R. E.; Culp, H. W. Mechanism of the dealkylation of tertiary amines by hepatic oxygenases. Stable isotope studies with 1-benzyl-4-cyano-4-phenylpiperidine. J. Med. Chem. 1979, 22, 1100-1103.
8. Mamada, K.; Kasuya, Y.; Baba, S. Pharmacokinetic equivalence of deuterium-labeled and unlabeled-phenytoin. Drug Metab. Dispos. 1986, 14, 509-511.
9. Najjar, S. E.; Blake, M. I.; Benoit, P. A.; Lu, M. C. Effects of deuteration on locomotor activity of amphetamine. J. Med. Chem. 1978, 21, 555-558.
10. Farmer, P. B.; Foster, A. B.; Jarman, M.; Oddy, M. R.; Reed, D. J. Synthesis, metabolism, and antitumor activity of deuterated analogues of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. J. Med. Chem. 1978, 21, 514-520.
11. Hoffman, J. M.; Habecker, C. N.; Pietruszkiewicz, A. M.; Bolhofer, W. A.; Cragoe, E. J.; Torchiana, M. L.; Hirschmann, R. A Deuterium isotope effect on the inhibition of gastric secretion by N,N-dimethyl-N′-[2-(diisopropylamino)ethyl]-N′- (4,6-dimethyl-2-pyridyl)urea. Synthesis of metabolites. J. Med. Chem. 1983, 26, 1650-1653.
12. A receptors. J. Med. Chem. 1998, 41, 1846-1854.
13. Guitton, J.; Desage, M.; Lepape, A.; Degoute, C. S.; Manchon, M.; Brazier, J. L. Quantitation of propofol in whole blood by gas chromatography-mass spectrometry. J. Chromatogr. B 1995, 669, 358-365.
14. Guitton, J.; Burronfosse, T.; Sanchez, M.; Desage, M. Quantitation of propofol metabolite, 2,6-diisopropyl-1,4-quinol, by gas chromatography-mass spectrometry. Anal. Lett. 1997, 30, 1369-1378.
15. Elbast, W.; Guitton, M.; Desage, M.; Deruaz, D.; Manchon, M.; Brazier, J. L. Comparison between gas chromatography-atomic emission detection and gas chromatography-mass spectrometry for assay of propofol. J. Chromatogr. B 1996, 686, 97-102.
16. Stetson, P. L.; Domino, E. F.; Sneyd, J. R. Determination of plasma propofol levels using gas chromatography-mass spectrometry with selected-ion monitoring. J. Chromatogr. B 1993, 620, 260-267.
17. Langenhove, A. V. Isotope effects: Definitions and consequences for pharmacological studies. J. Clin. Pharmacol. 1986, 26, 383-389.
18. Claesen, M.; Moustafa, M. A. A.; Adline, J.; Vandervorst, D.; Poupaert, J. H. Evidence for an arene oxide-NIH shift pathway in the metabolic conversion of phenytoin to 5-(4-hydroxyphenyl)- 5-phenylhydantoin in the rat and in man. Drug Metab. Dispos. 1982, 6, 667-671.
19. Darbyshire, J. F.; Iyer, K. R.; Grogan, J.; Korzekwa, K. R.; Trager, W. F. Selectively deuterated Warfarin. Substate probe for the mechanism of aromatic hydroxylation catalyzed by cytochrome P450. Drug Metab. Dispos. 1996, 24, 1038-1045.
20. Nelson, W. L.; Brück, R. T. Metabolism of β-adrenergic antagonists. Evidence for arene oxide-NIH shift pathway in the aromatic hydroxylation of oxprenolol. J. Med. Chem. 1988, 22, 1088-1092.
21. Anderson, A.; Belelli, D.; Bennett, D. J.; Buchanan, K. I.; Casula, A.; Cooke, A.; Feilden, H.; Gemmell, D. K.; Hamilton, N. M.; Hutchinson, E. J.; Lambert, J. J.; Maidment, M. S.; McGuire, R.; McPhail, P.; Miller, S.; Muntoni, A.; Peters, J. A.; Sansbury, F. H.; Stevenson, D.; Sundaram, H. α-Amino acid phenolic ester derivatives: Novel water-soluble general anesthetic agents which allosterically modulate gaba αreceptors. J. Med. Chem. 2001, 44, 3582-3591.
22. Mizutani, T.; Yamamoto, K.; Tajima, K. Isotope effects on the metabolism and pulmonary toxicity of butylated hydroxytoluene in mice by deuteration of the 4-methyl group. Toxicol. Appl. Pharmacol. 1983, 69, 283-290.