Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics

ACS Chemical Neuroscience

Volumn 8, Issue 7, 2017, Pages 1570-1576

  Raper, Jessica ^a   Morrison, Ryan D ^b   Daniels, J Scott ^b   Howell, Leonard ^a,c   Bachevalier, Jocelyne ^a   Wichmann, Thomas ^a,c   Galvan, Adriana ^a,c  

^a EMORY UNIVERSITY   (United States)

^b Sano Informed Prescribing   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

blood brain barrier; clozapine; DREADDs; pharmacokinetics; Rhesus macaque

Indexed keywords

CLOZAPINE; CLOZAPINE N OXIDE; NORCLOZAPINE; ABCG2 PROTEIN, HUMAN; BREAST CANCER RESISTANCE PROTEIN; CLOZAPINE N-OXIDE; MULTIDRUG RESISTANCE PROTEIN 1; NEUROLEPTIC AGENT; TUMOR PROTEIN;

ADULT; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DISTRIBUTION; DRUG METABOLISM; FEMALE; MALE; MAXIMUM PLASMA CONCENTRATION; MULTIPLE REACTION MONITORING; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; RHESUS MONKEY; TIME TO MAXIMUM PLASMA CONCENTRATION; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; CAPILLARY PERMEABILITY; CEREBROSPINAL FLUID; DOG; DOSE RESPONSE; DRUG EFFECTS; GENETIC TRANSFECTION; GENETICS; HUMAN; MDCK CELL LINE; METABOLISM; PRECLINICAL STUDY;

ANIMALS; ANTIPSYCHOTIC AGENTS; ATP BINDING CASSETTE TRANSPORTER, SUB-FAMILY G, MEMBER 2; ATP-BINDING CASSETTE, SUB-FAMILY B, MEMBER 1; BLOOD-BRAIN BARRIER; CAPILLARY PERMEABILITY; CLOZAPINE; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; FEMALE; HUMANS; MACACA MULATTA; MADIN DARBY CANINE KIDNEY CELLS; MALE; NEOPLASM PROTEINS; TRANSFECTION;

EID: 85024832815     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.7b00079     Document Type: Article

References (32)

1. Farrell, M. S. and Roth, B. L. (2013) Pharmacosynthetics: Reimagining the pharmacogenetic approach Brain Res. 1511, 6-20 10.1016/j.brainres.2012.09.043
2. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., and Roth, B. L. (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand Proc. Natl. Acad. Sci. U. S. A. 104, 5163-5168 10.1073/pnas.0700293104
3. Roth, B. L. (2016) DREADDs for Neuroscientists Neuron 89, 683-694 10.1016/j.neuron.2016.01.040
4. Smith, K. S., Bucci, D. J., Luikart, B. W., and Mahler, S. V. (2016) DREADDS: Use and application in behavioral neuroscience Behav. Neurosci. 130, 137-155 10.1037/bne0000135
5. Wess, J., Nakajima, K., and Jain, S. (2013) Novel designer receptors to probe GPCR signaling and physiology Trends Pharmacol. Sci. 34, 385-392 10.1016/j.tips.2013.04.006
6. Urban, D. J. and Roth, B. L. (2015) DREADDs (designer receptors exclusively activated by designer drugs): chemogenetic tools with therapeutic utility Annu. Rev. Pharmacol. Toxicol. 55, 399-417 10.1146/annurev-pharmtox-010814-124803
7. Rogan, S. C. and Roth, B. L. (2011) Remote control of neuronal signaling Pharmacol Rev. 63, 291-315 10.1124/pr.110.003020
8. Eldridge, M. A., Lerchner, W., Saunders, R. C., Kaneko, H., Krausz, K. W., Gonzalez, F. J., Ji, B., Higuchi, M., Minamimoto, T., and Richmond, B. J. (2016) Chemogenetic disconnection of monkey orbitofrontal and rhinal cortex reversibly disrupts reward value Nat. Neurosci. 19, 37-39 10.1038/nn.4192
9. Grayson, D. S., Bliss-Moreau, E., Machado, C. J., Bennett, J., Shen, K., Grant, K. A., Fair, D. A., and Amaral, D. G. (2016) The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala Neuron 91, 453-466 10.1016/j.neuron.2016.06.005
10. Nagai, Y., Kikuchi, E., Lerchner, W., Inoue, K. I., Ji, B., Eldridge, M. A., Kaneko, H., Kimura, Y., Oh-Nishi, A., Hori, Y., Kato, Y., Hirabayashi, T., Fujimoto, A., Kumata, K., Zhang, M. R., Aoki, I., Suhara, T., Higuchi, M., Takada, M., Richmond, B. J., and Minamimoto, T. (2016) PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation Nat. Commun. 7, 13605 10.1038/ncomms13605
11. Chang, W. H., Lin, S. K., Lane, H. Y., Wei, F. C., Hu, W. H., Lam, Y. W., and Jann, M. W. (1998) Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients Prog. Neuro-Psychopharmacol. Biol. Psychiatry 22, 723-739 10.1016/S0278-5846(98)00035-9
12. Jann, M. W., Lam, Y. W., and Chang, W. H. (1994) Rapid formation of clozapine in guinea-pigs and man following clozapine-N-oxide administration Arch. Int. Pharmacodyn. Ther. 328, 243-250
13. MacLaren, D. A., Browne, R. W., Shaw, J. K., Krishnan Radhakrishnan, S., Khare, P., Espana, R. A., and Clark, S. D. (2016) Clozapine N-Oxide Administration Produces Behavioral Effects in Long-Evans Rats: Implications for Designing DREADD Experiments eNeuro 3, ENEURO.0219-16.2016 10.1523/ENEURO.0219-16.2016
14. Kozorovitskiy, Y., Saunders, A., Johnson, C. A., Lowell, B. B., and Sabatini, B. L. (2012) Recurrent network activity drives striatal synaptogenesis Nature 485, 646-650 10.1038/nature11052
15. Bridges, T. M., Morrison, R. D., Byers, F. W., Luo, S., and Scott Daniels, J. (2014) Use of a novel rapid and resource-efficient cassette dosing approach to determine the pharmacokinetics and CNS distribution of small molecule 7-transmembrane receptor allosteric modulators in rat Pharmacol. Res. Perspect. 2, e00077 10.1002/prp2.77
16. Liu, X., Chen, C., and Smith, B. J. (2008) Progress in brain penetration evaluation in drug discovery and development J. Pharmacol. Exp. Ther. 325, 349-356 10.1124/jpet.107.130294
17. Xia, C. Q., Milton, M. N., and Gan, L. S. (2007) Evaluation of drug-transporter interactions using in vitro and in vivo models Curr. Drug Metab. 8, 341-363 10.2174/138920007780655423
18. Xiao, G., Black, C., Hetu, G., Sands, E., Wang, J., Caputo, R., Rohde, E., and Gan, L. S. (2012) Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates Drug Metab. Dispos. 40, 779-787 10.1124/dmd.111.043703
19. Hellman, K., Aadal Nielsen, P., Ek, F., and Olsson, R. (2016) An ex Vivo Model for Evaluating Blood-Brain Barrier Permeability, Efflux, and Drug Metabolism ACS Chem. Neurosci. 7, 668-680 10.1021/acschemneuro.6b00024
20. Bauer, B., Hartz, A. M., Fricker, G., and Miller, D. S. (2005) Modulation of p-glycoprotein transport function at the blood-brain barrier Exp Biol. Med. (Maywood) 230, 118-127
21. Miller, D. S. (2010) Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier Trends Pharmacol. Sci. 31, 246-254 10.1016/j.tips.2010.03.003
22. Zheng, Y., Chen, X., and Benet, L. Z. (2016) Reliability of In Vitro and In Vivo Methods for Predicting the Effect of P-Glycoprotein on the Delivery of Antidepressants to the Brain Clin. Pharmacokinet. 55, 143-167 10.1007/s40262-015-0310-2
23. Bickel, M. H. (1969) The pharmacology and biochemistry of N-oxides Pharmacol Rev. 21, 325-355
24. Lameh, J., Burstein, E. S., Taylor, E., Weiner, D. M., Vanover, K. E., and Bonhaus, D. W. (2007) Pharmacology of N-desmethylclozapine Pharmacol. Ther. 115, 223-231 10.1016/j.pharmthera.2007.05.004
25. Roth, B. L. and Driscoll, J. (2014) Psychoactive Drug Screening Program, National Institute of Mental Health, Bethesda, MD.
26. Canton, H., Verriele, L., and Colpaert, F. C. (1990) Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites Eur. J. Pharmacol. 191, 93-96 10.1016/0014-2999(90)94100-C
27. Seeman, P. and Van Tol, H. H. (1994) Dopamine receptor pharmacology Trends Pharmacol. Sci. 15, 264-270 10.1016/0165-6147(94)90323-9
28. Pardridge, W. M. (2012) Drug transport across the blood-brain barrier J. Cereb. Blood Flow Metab. 32, 1959-1972 10.1038/jcbfm.2012.126
29. Chen, X., Choo, H., Huang, X. P., Yang, X., Stone, O., Roth, B. L., and Jin, J. (2015) The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs ACS Chem. Neurosci. 6, 476-484 10.1021/cn500325v
30. Raper, J., Wilson, M., Sanchez, M., Machado, C. J., and Bachevalier, J. (2013) Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys Psychoneuroendocrinology 38, 1021-1035 10.1016/j.psyneuen.2012.10.008
31. Raper, J., Stephens, S. B., Henry, A., Villarreal, T., Bachevalier, J., Wallen, K., and Sanchez, M. M. (2014) Neonatal amygdala lesions lead to increased activity of brain CRF systems and hypothalamic-pituitary-adrenal axis of juvenile rhesus monkeys J. Neurosci. 34, 11452-11460 10.1523/JNEUROSCI.0269-14.2014
32. Kalvass, J. C., Maurer, T. S., and Pollack, G. M. (2007) Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein efflux ratios Drug Metab. Dispos. 35, 660-666 10.1124/dmd.106.012294