Structural features associated with reactive metabolite formation in clozapine analogues

Chemico-Biological Interactions

Volumn 104, Issue 2-3, 1997, Pages 117-129

  Uetrecht, Jack ^a   Zahid, Nasir ^a   Tehim, Ashik ^b   Mim Fu, J ^b   Rakhit, Suman ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b Allelix Biopharmaceuticals   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; CLOZAPINE DERIVATIVE; DRUG METABOLITE; FLUPERLAPINE; GLUTATHIONE; MYELOPEROXIDASE; OLANZAPINE;

AGRANULOCYTOSIS; ARTICLE; CONTROLLED STUDY; DRUG OXIDATION; DRUG STRUCTURE; HUMAN; HUMAN CELL; NEUTROPHIL;

AGRANULOCYTOSIS; ANTIPSYCHOTIC AGENTS; BENZODIAZEPINES; BINDING SITES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, LIQUID; CLOZAPINE; DIBENZAZEPINES; GLUTATHIONE; GRANULOCYTES; HUMANS; HYDROGEN PEROXIDE; HYPOCHLOROUS ACID; LYMPHOCYTE ACTIVATION; MASS SPECTROMETRY; NEUTROPHILS; NITROGEN; OXIDATION-REDUCTION; PEROXIDASE; PIRENZEPINE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0030913557     PISSN: 00092797     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0009-2797(97)00017-3     Document Type: Article

References (10)

1. J. Idanpaan-Heikkila, E. Alhava, M. Olkinuora and I.P. Palva, Agranulocytosis during treatment with clozapine, Eur. J. Clin. Pharmacol., 11 (1977) 193-198.
2. J.M. Alvir and J.A. Lieberman, A re-evaluation of the clinical characteristics of clozapine-induced agranulocytosis in light of the United States experience, J. Clin. Psychopharmacol., 14 (1994) 87-89.
3. H.H. Van Tol, J.R. Bunzow, H.C. Guan, et al., Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine, Nature, 350 (1991) 610-614.
4. L.R. Pohl, H. Satoh, D.D. Christ and J.G. Kenna, The immunologic and metabolic basis of drug hypersensitivities, Ann. Rev. Pharmacol., 28 (1988) 367-387.
5. J.P. Uetrecht, The role of leukocyte-generated metabolites in the pathogenesis of idiosyncratic drug reactions, Drug Metab. Rev., 24 (1992) 299-366.
6. Z.C. Liu and J.P. Uetrecht, Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells, J. Pharmacol. Exp. Ther., 275 (1995) 1476-1483.
7. J.P. Uetrecht, N. Zahid and D. Whitfield, Metabolism of vesnarinone by activated neutrophils; implications for vesnarinone-induced agranulocytosis, J. Pharmacol. Exp. Ther., 270 (1994) 865-872.
8. J.P. Uetrecht, H.M. Ma, E. MacKnight and R. McClelland, Oxidation of aminopyrine by hypochlorite to a reactive dication: possible implications for aminopyrine-induced agranulocytosis, Chem. Res. Toxicol., 8 (1995) 226-233.
9. A.E. Cribb, M. Miller, A. Tesoro and S.P. Spielberg, Peroxidase-dependent oxidation of sulfonamides by monocytes and neutrophils from humans and dogs, Mol. Pharmacol., 38 (1990) 744-751.
10. J.L. Maggs, M.D. Tingle, N.R. Kitteringham and B.K. Park, Drug-protein conjugates-XIV: mechanisms of formation of protein-arylating intermediates from amodiaquine, a myelotoxin and hepatoxin in man, Biochem. Pharmacol., 37 (1988) 303-311.