Regional distribution of clomipramine and desmethylclomipramine in rat brain and peripheral organs on chronic clomipramine administration

Journal of Psychopharmacology

Volumn 24, Issue 8, 2010, Pages 1261-1268

  Aitchison, K ^a   Datla, K ^b   Rooprai, H ^c   Fernando, J ^d   Dexter, D ^b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c MIDDLESEX UNIVERSITY   (United Kingdom)

^d VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

antidepressive agents; antineoplastic agents; cerebral cortex; clomipramine; rats; Sprague Dawley

Indexed keywords

CLOMIPRAMINE; NORCLOMIPRAMINE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CORTEX; BRAIN REGION; BRAIN STEM; CEREBELLUM; CHRONIC DRUG ADMINISTRATION; CORPUS STRIATUM; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG TISSUE LEVEL; HEART; HIPPOCAMPUS; HYPOTHALAMUS; KIDNEY; LIVER; LUNG; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; SPLEEN;

ANIMALS; ANTIDEPRESSIVE AGENTS, TRICYCLIC; BRAIN; CLOMIPRAMINE; MALE; RATS; RATS, SPRAGUE-DAWLEY; TIME FACTORS; TISSUE DISTRIBUTION;

EID: 77955164691     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881109105789     Document Type: Article

References (56)

1. Avella, J., Lehrer, M., Katz, M., Minden, E. (2004) Two cases involving clomipramine intoxication. J Anal Toxicol 28: 504-508.
2. Balant-Gorgia, AE, Balant, LP, Garrone, G. (1989) High blood concentrations of imipramine or clomipramine and therapeutic failure: a case report study using drug monitoring data. Ther Drug Monit 11: 415-420.
3. Balant-Gorgia, AE, Balant, LP, Genet, CH, Dayer, P., Aeschlimann, JM, Garrone, G. (1986) Importance of oxidative polymorphism and levomepromazine treatment on the steady-state blood concentrations of clomipramine and its major metabolites. Eur J Clin Pharmacol 31: 449-455.
4. Balant-Gorgia, AE, Gex-Fabry, M., Balant, LP (1991) Clinical pharmacokinetics of clomipramine. Clin Pharmacokinet 20: 447-462.
5. Basu, A., Tsapakis, EM, Aitchison, KJ (2004) Pharmacogenetics and psychiatry. Curr Psychiatry Rep 6: 134-142.
6. Bertilsson, L., Dahl, ML (1996) Polymorphic drug oxidation. Relevance to the treatment of psychiatric disorders. CNS Drugs 5: 200-222.
7. Bertilsson, L., Dahl, ML, Sjöqvist, F., à...berg-Wistedt, A., Humble, M., Johansson, I. (1993) Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine [letter]. Lancet 341: 63.
8. Bickel, MH, Brochon, R., Friolet, B., Herrmann, B., Stofer, AR (1967) Clinical and biochemical results of a fatal case of desipramine intoxication. Psychopharmacologia 10: 431-436.
9. Bolo, NR, Hode, Y., Nedelec, JF, Laine, E., Wagner, G., Macher, JP (2000) Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. Neuropsycopharmacology 23: 428-438.
10. Daley, E., Wilkie, D., Loesch, A., Hargreaves, IP, Kendall, DA, Pilkington, GJ (2005) Chlorimipramine: a novel anticancer agent with a mitochondrial target. Biochem Biophys Res Commun 328: 623-632.
11. Danish University Antidepressant Group (DUAG) (1999) Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Clin Pharmacol Ther 66: 152-165.
12. Della Corte, L., Sgaragli, GP (1984) Tissue distribution of chlorimipramine and its desmethylated metabolite after a single dose in the rat. Pharmacol Res Commun 16: 207-213.
13. DeLisi, LE, Bertisch, H. (2006) A preliminary comparison of the hopes of researchers, clinicians, and families for the future ethical use of genetic findings on schizophrenia. Am J Med Genet B Neuropsychiatr Genet 141: 110-115.
14. Friedman, E., Cooper, TB (1983) Pharmacokinetics of chlorimipramine and its demethylated metabolite in blood and brain regions of rats treated acutely and chronically with chlorimipramine. J Pharmacol Exp Ther 225: 387-390.
15. Fujita, K., Kobashi, A., Suzuki, S., Nakazawa, K. (1991) Changes of serotonin and catecholamines are related to pharmacokinetic alterations of clomipramine in rat brain. Eur J Pharmacol 204: 227-233.
16. Glotzbach, KR, Preskorn, SH (1982) Brain concentrations of tricyclic antidepressants: single-dose kinetics and relationship to plasma concentrations in chronically dosed rats. Psychopharmacol 78: 25-27.
17. Hiroi, T., Imaoka, S., Chow, T., Funae, Y. (1998) Tissue distributions of CYP2D1, 2D2, 2D3, and 2D4 mRNA in rats detected by RT-PCR. Biochim Biophys Acta 1380: 305-312.
18. Huezo-Diaz, P., Perroud, N., Spencer, E., Smith, R., Sim, S., Virding, S., et al. (Submitted) Effect of CYP2C19 variants including the CYP2C19*17 allele on steadystate escitalopram level in depressed subjects: a prospective study.
19. Kawashima, H., Sequeira, DJ, Nelson, DR, Strobel, HW (1996) Genomic cloning and protein expression of a novel rat brain cytochrome P-450 CYP2D18 catalyzing imipramine N-demethylation. J Biol Chem 271: 28176-28180.
20. Kirchheiner, J., Nickchen, K., Bauer, M., Wong, M-L., Licinio, J., Roots, I., et al. (2004) Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiat 9: 442-473.
21. Kurata, K., Kishatani, K., Kido, H., Kurachi, M., Yamaguchi, N. (1986) A pharmacokinetic study of clomipramine in regions of the brain. Jpn J Psychiatry Neurol 40: 631-638.
22. Kurata, K., Kurachi, M., Tanii, Y. (1988) Distribution of clomipramine in various brain regions of rat under steady-state serum concentrations. Psychopharmacology 95: 167-170.
23. Levkovitz, Y., Gil-Ad, I., Zeldich, E., Dayag, M., Weizman, A. (2005) Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci 27: 29-42.
24. Marcourakis, T., Gorenstein, C., Ramos, RT, da Motta Singer, J. (1999) Serum levels of clomipramine and desmethyclomipramine and clinical improvement in panic disorders. J Psychopharmacol 13: 40-44.
25. Matsunaga, E., Zanger, UM, Hardwick, JP, Gelboin, HV, Meyer, UA, Gonzalez, FJ (1989) The CYP2D gene subfamily: analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats. Biochem 28: 7349-7355.
26. Mavissakalian, MR, Jones, B., Olson, S., Perel, J. (1990) Clomipramine in obsessive compulsive disorder. Clinical response and plasma levels. J Clin Pharmacol 10: 261-268.
27. Meredith, EJ, Holder, MJ, Chamba, A., Challa, A., Drake-Lee, A., Bunce, CM, et al. (2005) The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB J 19: 1187-1189.
28. Merry, S., Hamilton, TG, Flanigan, P., Freshney, RI, Kaye, SB (1991) Circumvention of pleitropic drug resistance in subcutaneous tumours in vivo with verapamil and clomipramine. Eur J Cancer 27: 31-34.
29. Nagy, A. (1997) Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats. J Pharm Pharmacol 29: 104-107.
30. Niznik, HB, Tyndale, RF, Sallee, FR, Gonzalez, FJ, Hardwick, JP, Inaba, T., et al. (1990) The dopamine transporter and cytochrome P45OIID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins. Arch Biochem Biophys 276: 424-432.
31. Pariante, CM, Hye, A., Williamson, R., Makoff, A., Lovestone, S., Kerwin, RW (2003) The antidepressant clomipramine regulates cortisol intracellular concentrations and glucocorticoid receptor expression in fibroblasts and rat primary neurones. Neuropsychopharmacology 28: 1553-1561.
32. Peters, MD, Davis, SK, Austin, S. (1990) Clomipramine: an antiobsessional tricyclic antidepressant. Clin Pharm 9: 165-178.
33. Pilkington, GJ, Akinwumni, J., Amar, S. (2006) The role of tricyclic drugs in selective triggering of mitochondrially-mediated apoptosis in neoplastic glia: a therapeutic option in malignant glioma ? Radiol Oncol 40: 73-85.
34. Pilkington, GJ, Parker, K., Murray, SA (2008) Approaches to mitochondrially-mediated cancer therapy. Seminars Cancer Biol 18: 226-235.
35. Pommerenke, EW, Volm, M. (1995) Reversal of doxorubicin-resistance in solid tumours by clomipramine. In Vivo 9: 99-102.
36. Rooprai, HK, Christidou, M., Pilkington, GJ (2003) The potential for strategies using micronutrients and heterocyclic drugs to treat invasive gliomas. Acta Neurochir 145: 683-690.
37. Sauter, C. (1989) Cytostatic activity of commonly used tricyclic antidepressants. Oncology 46: 155-157.
38. Sgaragli, GP, Valoti, M., Palmi, M., Frosni, M., Giovanni, MG, Bianchi, L., et al. (1995) Rat tissue concentrations of clomipramine, chlorpromazine and their N-demethylated metabolites after a single oral dose of the parent compound. J Pharm Pharmacol 47: 782-790.
39. Siegle, I., Fritz, P., Eckhardt, K., Zanger, UM, Eichelbaum, M. (2001) Cellular localisation and regional distribution of CYP2D6 mRNA and protein expression in human brain. Pharmacogenetics 11: 237-245.
40. Sim, SC, Risinger, C., Dahl, ML, Aklillu, E., Christensen, M., Bertilsson, L., et al. (2006) A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79: 103-113.
41. Shimoda, K., Noguchi, T., Ozeki, Y., Morita, S., Shibasaki, M., Someya, T., et al. (1995) Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation, desmethylation, and glucuronidation. Neuropsychopharmacology 12: 323-333.
42. Steingart, AB, Cotterchio, M. (1995) Do antidepressants cause, promote, or inhibit cancers? Clin Epidemiol 48: 1407-1412.
43. Suhara, T., Sudo, Y., Okubo, Y., Fukuda, H., Obata, T., Yoshikawa, K., et al. (1998) Lung as a reservoir for antidepressants in pharmacokinetic drug interactions. Lancet 351: 332-335.
44. Sugden, K., Tichopad, A., Khan, N., Craig, IW, DgSouza, UM Genes within The Serotonergic System Are Differentially Expressed In Human Brain. BMC Neuroscience, in press.
45. Sunshine, I., Baeumler, J. (1963) A fatal case of poisoning with amitriptyline. Nature. 199: 1103-1104.
46. Taylor, D., Paton, C., Kerwin, R. (2007) The Maudsley Prescribing Guidelines. Ninth edition. Abingdon, UK: Taylor & Francis.
47. Theurillat, R., Thormann, W. (1998) Monitoring of tricyclic antidepressants in human serum and plasma by HPLC: characterization of a simple, laboratory developed method via external quality assessment. J Pharm Biomed Anal 18: 751-760. (Pubitemid 29057805)
48. Thompson, CM, Kawashima, H., Strobel, HW (1998) Isolation of partially purified P450 2D18 and characterization of activity toward the tricyclic antidepressants imipramine and desipramine. Arch Biochem Biophys 359: 115-121.
49. Trimble, MR (1990) Worldwide use of clomipramine. J Clin Psychiat 51 (Suppl.). 51-54.
50. Tsuruo, T., Iida, H., Nojiri, M., Tsukagoshi, S., Sakurai, Y. (1983) Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine. J Pharm Dyn 6: 145-147.
51. von Bahr, C., Movin, G., Nordin, C., Lidén, A., Hammarlaund-Udenaes, M. (1991) Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype. Clin Pharmacol Ther 49: 234-240.
52. Weigmann, H., Hartter, S., Bagli, M., Hiemke, C. (2000) Steady state concentrations of clomipramine and its major metabolite desmethylclomipramine in rat brain and serum after oral administration of clomipramine. Eur Neuropsychopharmacol 10: 401-405.
53. Wu, Z-L., Huang, S-L., Ou-Yang, D-S., Xu, Z-H., Xie, H-G., Zhou, H-H. (1998) Clomipramine N-demethylation metabolism in human liver microsomes. Acta Pharmacologica Sinica 19: 433-436.
54. Xia, Z., Bergstrand, A., DePierre, JW, Nässberger, L. (1999) The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia LH-60 cells via caspase-3 activation. J Biochem Toxicol 13: 338-347.
55. Yamamoto, Y., Tasaki, T., Nakamura, A., Iwata, H., Kazusaka, A., Gonzalez, FJ, et al. (1998) Molecular basis of the Dark Agouti rat drug oxidation polymorphism: importance of CYP2D1 and CYP2D2. Pharmacogenetics 8: 73-82.
56. Yau, LW, Noble, J., Thomas, S., Kerwin, R., Morgan, PE, Lightman, S., et al. (2007) The antidepressant desipramine requires the ABCB1 (MDR-1)-type p-glycoprotein to upregulate the glucocorticoid receptor in mice. Neuropsychopharmacology 32: 2520-2529.