Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: A suggested solution based on in vivo occupancy

Journal of Pharmacology and Experimental Therapeutics

Volumn 305, Issue 2, 2003, Pages 625-631

  Kapur, Shitij ^a,b   Vanderspek, Susan C ^a   Brownlee, Barbara A ^a   Nobrega, José N ^a,b  

^a CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; DOPAMINE 2 RECEPTOR; HALOPERIDOL; NEUROLEPTIC AGENT; OLANZAPINE; QUETIAPINE; RISPERIDONE;

ANIMAL TISSUE; ARTICLE; CLINICAL STUDY; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG HALF LIFE; DRUG INFUSION; DRUG RECEPTOR BINDING; DRUG SOLUBILITY; EXPERIMENTAL MODEL; IN VIVO STUDY; INJECTION; MALE; MULTIPLE DRUG DOSE; NONHUMAN; OSMOTIC MINIPUMP; PRIORITY JOURNAL; RAT; RECEPTOR OCCUPANCY; SINGLE DRUG DOSE; SPECIES COMPARISON;

ANIMALS; ANTIPSYCHOTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; HALF-LIFE; HUMANS; INFUSION PUMPS; INJECTIONS, SUBCUTANEOUS; MALE; MENTAL DISORDERS; MODELS, PSYCHOLOGICAL; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, DOPAMINE D2; SPECIES SPECIFICITY;

EID: 0037405871     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.102.046987     Document Type: Article

References (27)

1. Aravagiri M, Ames D, Wirshing WC, and Marder SR (1997) Plasma level monitoring of olanzapine in patients with schizophrenia: determination by high-performance liquid chromatography with electrochemical detection. Ther Drug Monit 19:307-313.
2. Arnt J, Skarsfeldt T, and Hyttel J (1997) Differentiation of classical and novel antipsychotics using animal models. Int Clin Psychopharmacol 12 (Suppl 1):S9-S17.
3. Baldessarini RJ, Centorrino F, Flood JG, Volpicelli SA, Huston-Lyons D, and Cohen BM (1993) Tissue concentrations of clozapine and its metabolites in the rat. Neuropsychopharmacology 9:117-124.
4. Bezchlibnyk-Butler KZ and Jeffries JJ (1999) Clinical Handbook of Psychotropic Drugs. Hogrefe & Huber Publishers, Toronto.
5. Bressan RA, Jones HM, Ell PJ, and Pilowsky LS (2001) Dopamine D(2) receptor blockade in schizophrenia. Am J Psychiatry 158:971-972.
6. Burki HR (1986) Effects of fluperlapine on dopaminergic systems in rat brain. Psychopharmacology 89:77-84.
7. Campbell A, Herschel M, Cohen BM, and Baldessarini RJ (1980) Tissue levels of haloperidol by radioreceptor assay and behavioral effects of haloperidol in the rat. Life Sci 27:633-640.
8. Cheng YF and Paalzow LK (1992) Linear pharmacokinetics of haloperidol in the rat. Biopharm Drug Dispos 13:69-76.
9. Citrome L and Volavka J (2002) Optimal dosing of atypical antipsychotics in adults: a review of the current evidence. Harv Rev Psychiatry 10:280-291.
10. Farde L, Wiesel FA, Halldin C, and Sedvall G (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71-76.
11. Kapur S, Barlow K, VanderSpek SC, Javanmard M, and Nobrega JN (2001) Drug-induced receptor occupancy: substantial differences in measurements made in vivo vs ex vivo. Psychopharmacology (Berl) 157:168-171.
12. Kapur S and Remington G (2001) Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biol Psychiatry 50:873-883.
13. Kapur S, Wadenberg ML, and Remington G (2000a) Are animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the bench. Can J Psychiatry 45:241-246.
14. Kapur S, Zipursky R, Jones C, Remington G, and Houle S (2000b) Relationship between dopamine D(2) occupancy, clinical response and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514-520.
15. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, and Seeman P (2000c) A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 57:553-559.
16. Kapur S, Zipursky RB, and Remington G (1999) Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone and olanzapine in schizophrenia. Am J Psychiatry 156:286-293.
17. Lipska BK and Weinberger DR (2000) To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 23:223-239.
18. Nyberg S and Farde L (2000) Non-equipotent doses partly explain differences among antipsychotics - implications of PET studies [comment]. Psychopharmacology (Berl) 148:22-23.
19. Olsson H and Farde L (2001) Potentials and pitfalls using high affinity radioligands in PET and SPET determinations on regional drug induced D2 receptor occupancy - a simulation study based on experimental data. Neuroimage 14:936-945.
20. Rowland M and Tozer TN (1995) Clinical Pharmacokinetics: Concepts and Applications. Lippincott Williams & Wilkins, Philadelphia.
21. Saller CF and Salama AI (1993) Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology 112:285-292.
22. Schmitt U, Dahmen N, Fischer V, Weigmann H, Rao ML, Reuss S, and Hiemke C (1999) Chronic oral haloperidol and clozapine in rats: a behavioral evaluation. Neuropsychobiology 39:86-91.
23. Schotte A, Janssen PFM, Gommeren W, Luyten WHML, VanGompel P, Lesage AS, DeLoore K, and Leysen JE (1996) Risperidone compared with new and reference antipsychotic drugs; in vitro and in vivo receptor binding. Psychopharmacology 124:57-73.
24. Tauscher J and Kapur S (2001) Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies. CNS Drugs 15:671-678.
25. van Beijsterveldt LE, Geerts RJ, Leysen JE, Megens AA, Van den Eynde HM, Meuldermans WE, and Heykants JJ (1994) Regional brain distribution of risperidone and its active metabolite 9-hydroxy-risperidone in the rat. Psychopharmacology (Berl) 114:53-62.
26. Wadenberg ML, Kapur S, Soliman A, Jones C, and Vaccarino F (2000) Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats. Psychopharmacology (Berl) 150:422-429.
27. Zhang W and Bymaster FP (1999) The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors. Psychopharmacology (Berl) 141:267-278.