Positron emission tomographic analysis of dose-dependent MDL 100,907 binding to 5-hydroxytryptamine-2A receptors in the human brain

Journal of Clinical Psychopharmacology

Volumn 18, Issue 4, 1998, Pages 317-323

  Andrée, Bengt ^a   Nyberg, Svante ^a   Ito, Hiroshi ^a   Ginovart, Nathalie ^a   Brunner, Françoise ^b   Jaquet, Françoise ^b   Halldin, Christer ^a   Farde, Lars ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

3 METHYLSPIPERONE C 11; ALPHA (2,3 DIMETHOXYPHENYL) 1 [2 (4 FLUOROPHENYL)ETHYL] 4 PIPERIDINEMETHANOL; SEROTONIN 2A ANTAGONIST; SEROTONIN 2A RECEPTOR;

ARTICLE; BLOOD BRAIN BARRIER; CLINICAL TRIAL; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG RECEPTOR BINDING; HUMAN; HUMAN EXPERIMENT; MALE; NEOCORTEX; NORMAL HUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RECEPTOR OCCUPANCY;

BINDING, COMPETITIVE; BRAIN MAPPING; CEREBRAL CORTEX; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; FLUOROBENZENES; HUMANS; MALE; METABOLIC CLEARANCE RATE; PIPERIDINES; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTORS, SEROTONIN; REFERENCE VALUES; SEROTONIN ANTAGONISTS; TOMOGRAPHY, EMISSION-COMPUTED;

EID: 0031928090     PISSN: 02710749     EISSN: None     Source Type: Journal    
DOI: 10.1097/00004714-199808000-00012     Document Type: Article

References (30)

1. 2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 1992;49:538-44.
2. Csernansky JG, Poscher M, Faull KF. Serotonin in schizophrenia. In: Coccaro EF, Murphy DL, eds. Serotonin in major psychiatric disorders. Washington, DC: American Psychiatric Press, Inc., 1990:209-30.
3. Schmidt CJ, Sorensen SM, Kehne JH, Carr AA, Palfreyman MG. The role of 5-HT2A receptors in antipsychotic activity. Life Sci 1995;56:2209-22.
4. Breier A. Serotonin, schizophrenia and antipsychotic drug action. Schizophr Res 1995;14:187-202.
5. 2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 1989;25:390-2.
6. Casey DE. Serotonergic aspects of acute extrapyramidal syndromes in nonhuman primates. Psychopharmacol Bull 1989;25: 457-9.
7. Gerlach J. New antipsychotics: classification, efficacy, and adverse effects. Schizophr Bull 1991;17:289-309.
8. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and Serotonin2 pKi values. J Pharmacol Exp Ther 1989;251:238-46.
9. Nordström A-L, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G. D1-, D2 and 5HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 1995;152:1444-9.
10. Kehne JH, Baron BM, Carr AA, Chaney S, Elands J, Fledman DJ, Frank RA, van Giersbergen PLM, McCloskey TC, Johnson MP, McCarty DR, Poirot M, Senyah Y, Siegel BW, Corinne W. Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5HT2A antagonist with a favorable CNS safety profile. J Pharmacol Exp Ther 1996;277:968-81.
11. Sorensen SM, Kehne JH, Fadayel GM, Humphreys TM, Ketteler HJ, Sullivan CK, Taylor VL, Schmidt CJ. Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies. J Pharmacol Exp Ther 1993;266:684-91.
12. Lyon RA, Titeler M, Frost JJ, Whitehouse PJ, Wong DF, Wagner HN Jr, Dannals RF, Links JM, Kuhar MJ. 3H-3-N-methylspiperone labels D2 dopamine receptors in basal ganglia and S2 serotonin receptors in cerebral cortex. J Neurosci 1986;6:2941-9.
13. Baldessarini RJ, Kula NS, Campbell A, Bakthavachalam V, Yuan J, Neumeyer JL. Prolonged D2 antidopaminergic activity of alkylating and nonalkylating derivatives of spiperone in rat brain. Mol Pharmacol 1992;42:856-63.
14. Nyberg S, Farde L, Halldin C. A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in healthy subjects. Neuropsychopharmacology 1997;16:1-7.
15. Barnes TRE. A rating scale for drug-induced akathisia. Br J Psychiatry 1989;154:672-6.
16. Nyberg S, Farde L, Eriksson L, Halldin C. 5HT2 and D2 dopamine receptor occupancy in the living human brain: a PET-study with risperidone. Psychopharmacology (Berl) 1993;110:265-72.
17. Wienhard K, Dahlbom M, Eriksson L, Michel C, Bruckbauer T, Pietrzyk U, Heiss W. The ECAT EXACT HR: performance of a new high resolution positron scanner. J Comput Assist Tomogr 1994; 18:110-8.
18. Wong D, Wagner H, Dannals R, Links J, Frost J, Ravert H, Wilson A, Rosenbaum A, Gjedde A, Douglass K, Petronis J, Folstein M, Toung J, Burns H, Kuhar M. Effects of age on dopamine and serotonin receptors measured by positron emission tomography in the living human brain. Science 1984;226:1393-6.
19. Schotte A, Maloteaux JM, Laduron PM. Characterization and regional distribution of serotonin S2-receptors in human brain. Brain Res 1983;276:231-5.
20. Pazos A, Probst A, Palacios JM. Serotonin receptors in the human brain - IV. Autoradiographic mapping of serotonin-2 receptors. Neuroscience 1987;21:123-39.
21. Farde L, Nyberg S, Oxenstierna G, Nakashima Y, Halldin C, Ericsson B. PET studies on D2 and 5HT2 receptor binding in risperidone treated schizophrenic patients. J Clin Psychopharmacol 1995;15:19S-23S.
22. Nakashima Y, Farde L. Comparison of currently applied methods for PET quantification of specific [11C]raclopride binding. J Cereb Blood Flow Metab 1995;15[suppl 1]:S643.
23. Karlsson P, Farde L, Halldin C, Sedvall G, Ynddal L, Sloth-Nielsen M. Oral administration of NNC 756 - a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man. Psychopharmacology (Berl) 1995;119:1-8.
24. Gründer G, Yokoi F, Offord SJ, Ravert HT, Dannals RF, Salzmann JK, Szymanski S, Wilson PD, Howard DR, Wong DF. Time course of 5-HT2A receptor occupancy in the human brain after a single oral dose of the putative antipsychotic drug MDL 100,907 measured by positron emission tomography. Neuropsychopharmacology 1997;17:175-85.
25. Schotte A, Janssen PMF, Gommeren W, Luyten WHML, Van Gompel P, Lesage AS, De Loore K, Leysen JE. Risperidone compared with new and reference antipsychotic drugs - in vitro and in vivo receptor binding. Psychopharmacology (Berl) 1996;124:57-73.
26. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 1996;14:87-96.
27. 18F-labeled setoperone. J Neurochem 1990; 54:1744-54.
28. Crouzel C, Guillaume M, Barré L, Lemaire C, Pike VW. Ligands and tracers for PET studies on the 5HT system - current status. Int J Rad Appl Instrum B 1992;19:857-70.
29. Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn C, Carr A, Brunner F, Farde L. [11C]MDL 100907, a radioligand for selective imaging of 5-HT2A receptors with positron emission tomography. Life Sci 1996;58:PL (187-192).
30. Ito H, Nyberg S, Halldin C, Lundkvist C, Farde L. PET imaging of central 5-HT2A receptors with carbon-11-MDL 100,907. J Nucl Med 1998;39:208-14.