Journal ArticleDOI
Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency.
Peroutka Sj,Synder Sh +1 more
TLDR
The authors examined the potencies of 22 neuroleptic drugs competing for binding sites associated with dopamine, serotonin, alpha-adrenergic, and histamine receptors in brain membranes and found that although many neuroleptics are quite potent in competing at several receptor sites, the average antipsychotic clinical potency correlates closely only with the drug affinity for dopamine receptors labeled by 3H-spiroperidol.Abstract:
The authors examined the potencies of 22 neuroleptic drugs competing for binding sites associated with dopamine, serotonin, alpha-adrenergic, and histamine receptors in brain membranes. They found that although many neuroleptics are quite potent in competing at several of these receptor sites, the average antipsychotic clinical potency correlates closely only with the drug affinity for dopamine receptors labeled by 3H-spiroperidol At clinically effective doses, however, substantial occupancy of serotonin, alpha-adrenergic, and histamine receptors often occurs and may account for some of the auxiliary actions of neuroleptics.read more
Citations
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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.
Journal ArticleDOI
Dopamine in Schizophrenia: A Review and Reconceptualization
TL;DR: The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms) and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.
Journal ArticleDOI
Positron Emission Tomographic Analysis of Central D1 and D2 Dopamine Receptor Occupancy in Patients Treated With Classical Neuroleptics and Clozapine: Relation to Extrapyramidal Side Effects
Lars Farde,Anna-Lena Nordström,Frits-Axel Wiesel,Stefan Pauli,Christer Halldin,Göran Sedvall +5 more
TL;DR: This finding indicates that neuroleptic-induced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia of drug-treated schizophrenic patients and demonstrates that clozapine is also "atypical" with respect to the central D1 occupancy in patients.
Journal ArticleDOI
Radioreceptor binding profile of the atypical antipsychotic olanzapine
Frank P. Bymaster,David O. Calligaro,Julie F. Falcone,Richard D Marsh,Nicholas A. Moore,Nicholas C Tye,Philip Seeman,David T. Wong +7 more
TL;DR: The receptor binding profile of olanzapine is consistent with the antidopaminergic, antiserotonergic, and antimuscarinic activity observed in animal models and predicts atypical antipsychotic activity in man.
Journal ArticleDOI
Quantitative Analysis of D2 Dopamine Receptor Binding in the Living Human Brain by PET
TL;DR: Studies of [11C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients.
References
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Journal ArticleDOI
Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs
TL;DR: Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding, providing a simple in vitro means for evaluating new drugs as potential antischizophrenic agents.
Journal ArticleDOI
Antipsychotic drug doses and neuroleptic/dopamine receptors
TL;DR: It is reported here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.
Journal Article
Multiple Serotonin Receptors: Differential Binding of [3H]5-Hydroxytryptamine, [3H]Lysergic Acid Diethylamide and [3H]Spiroperidol
TL;DR: It is proposed that [3H]5-HT and[3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5- HT2 receptors, respectively.
Journal ArticleDOI
Brain receptors for antipsychotic drugs and dopamine: direct binding assays.
TL;DR: Various antipsychotic drugs inhibited this stereospecific component in both the dopamine and haloperidol assays, and these inhibitory potencies correlated with the clinical doses used for controlling schizophrenia.
Journal ArticleDOI
Serotonergic component of neuroleptic receptors
TL;DR: It is suggested that serotonergic, as well as dopamine agonists or antagonists for rat frontal cortex and striatal receptors are involved in the mechanism of action of neuroleptic drugs.
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Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs
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Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain.
Arvid Carlsson,Margit Lindqvist +1 more