Journal ArticleDOI
Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol
Hans Karbe,Klaus Wienhard,Kurt Hamacher,Michael Huber,Karl Herholz,Heinz H. Coenen,Gerhard Stöcklin,A. Lövenich,W.-D. Heiss +8 more
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TLDR
The study shows for the first time in humans that striatal MSP binding reflects the different D2 dopamine receptor affinities of clozapine and haloperidol.Abstract:
Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using (18F)fluorodeoxyglucose (FDG) and (18F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450 mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drug-free male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D2 dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D2 dopamine receptor affinities of clozapine and haloperidol.read more
Citations
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Dopamine receptor pharmacology
TL;DR: Although antipsychotic drugs originally helped to discover dopamine receptors, the five dopamine receptors presently identified and cloned are facilitating the search for and discovery of more selective antipsychotics and antiparkinson drugs.
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Atypical Antipsychotics: Mechanism of Action:
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Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors
TL;DR: The atypical neuroleptics remoxipride, clozapine, perlapine, seroquel, and melperone had low affinity for the dopamine D2 receptor (radioligand-independent dissociation constants of 30 to 90 nM), which makes these latter five drugs readily displaceable by high levels of endogenous dopamine in the caudate or putamen.
References
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Journal ArticleDOI
Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine
TL;DR: In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.
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Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.
TL;DR: The D3 receptor is localized to limbic areas of the brain, which are associated with cognitive, emotional and endocrine functions, and seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease.
Journal ArticleDOI
Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
Hubert H.M. Van Tol,James R. Bunzow,Hong-Chang Guan,Roger K. Sunahara,Philip Seeman,Hyman B. Niznik,Olivier Civelli +6 more
TL;DR: The cloning of a gene that encodes a dopamine receptor gene that has high homology to the human dopamine D2 and D3 receptor genes is reported, which suggests the existence of other types of dopamine receptors which are more sensitive to clozapine.
Journal ArticleDOI
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1
Roger K. Sunahara,Hong-Chang Guan,Brian F. O'Dowd,Philip Seeman,Lisanne G. Laurier,Gordon Y.K. Ng,Susan R. George,J. Torchia,H. H. M. Van Tol,Hyman B. Niznik +9 more
TL;DR: The cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned Dt receptor is reported here the existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.
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Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain
TL;DR: Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidols, which may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.