0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Clozapine and Dopamine D2 Blockade
LYN S. PILOWSKY, PH.D., M.R.C.PSYCH.; PETER J. ELL, M.D., M.SC., P.D., F.R.C.R., F.R.C.P.
Am J Psychiatry 2002;159:324-a-325. doi:10.1176/appi.ajp.159.2.324-a

To the Editor: Mirjam Talvik, M.D., et al. (1) asserted that there is "no support" for the regionally selective action of clozapine at dopamine D2 receptors. Much evidence contradicts this view. Chronic treatment with clozapine (in contrast to treatment with classical antipsychotic drugs) up-regulates cortical D2 receptors at doses that do not affect striatal receptors. Dopamine turnover is also increased by clozapine in the cortex but not in the striatum (2). Our [123I]epidepride single photon emission computerized tomography (SPECT) studies have shown that clozapine preferentially blocks temporal cortical, over striatal D2, receptors. D2 occupancy by classical antipsychotic drugs has been shown as not regionally selective (3). Dr. Talvik and colleagues suggested methods limitations (which we discuss comprehensively) in our earlier studies, rendering these findings inconclusive. Nevertheless, they did not cite two short positron emission tomography (PET) reports. These independent studies, using fully validated, long-lived PET probes and quantitative single-tracer PET protocols—[76Br]FLB 457 and [18F]epidepride—have substantiated our data for clozapine and olanzapine, respectively (4, 5). Dr. Talvik et al. (1) now supply findings to the contrary. The reason for discrepant results awaits elucidation. Possibilities include variability in ligand kinetics, the sensitivity of different ligands to regional dopamine concentrations, or receptor status. The majority of in vitro animal and human data still favor a selective action of clozapine at limbic cortical D2 receptors. This issue remains unresolved in vivo, to be clarified by further studies.

Talvik M, Nordström A-L, Nyberg S, Olsson H, Halldin C, Farde L: No support for regional selectivity in clozapine-treated patients: a PET study with [11C]raclopride and [11C]FLB 457. Am J Psychiatry  2001; 158:926-930
[PubMed]
 
Lidow MS, Williams GV, Goldman-Rakic PS: The cerebral cortex: a case for a common site of action of antipsychotics. Trends Pharmacol Sci  1998; 19:136-140
[PubMed]
[CrossRef]
 
Bigliani V, Pilowsky LS: The in vivo neuropharmacology of schizophrenia. Br J Psychiatry 1999; 174(suppl 38):23-34
 
Xiberas X, Martinot JL, Mallet L, Artiges E, Loc’H C, Maziere B, Paillere-Martinot ML: Extrastriatial and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry  2001; 179:503-508
[PubMed]
[CrossRef]
 
Meltzer HY, Park S, Kessler R: Cognition, schizophrenia, and the atypical antipsychotic drugs. Proc Natl Acad Sci  1999; 96:13591-13593
[PubMed]
[CrossRef]
 
+

References

Talvik M, Nordström A-L, Nyberg S, Olsson H, Halldin C, Farde L: No support for regional selectivity in clozapine-treated patients: a PET study with [11C]raclopride and [11C]FLB 457. Am J Psychiatry  2001; 158:926-930
[PubMed]
 
Lidow MS, Williams GV, Goldman-Rakic PS: The cerebral cortex: a case for a common site of action of antipsychotics. Trends Pharmacol Sci  1998; 19:136-140
[PubMed]
[CrossRef]
 
Bigliani V, Pilowsky LS: The in vivo neuropharmacology of schizophrenia. Br J Psychiatry 1999; 174(suppl 38):23-34
 
Xiberas X, Martinot JL, Mallet L, Artiges E, Loc’H C, Maziere B, Paillere-Martinot ML: Extrastriatial and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry  2001; 179:503-508
[PubMed]
[CrossRef]
 
Meltzer HY, Park S, Kessler R: Cognition, schizophrenia, and the atypical antipsychotic drugs. Proc Natl Acad Sci  1999; 96:13591-13593
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 1

Related Content
Books
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 34.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 20.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 20.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 34.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
PubMed Articles
[Treatment-resistant schizophrenia]. Rev Med Brux 2014 May-Jun;35(3):169-73.