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New Insights into the Biology of Schizophrenia through the Mechanism of Action of Clozapine

Data up to Jan 2025

Published1995
Citations173
References387

Total Citations Per Year

Abstract

References (387)

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Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain.

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Differential induction of neurotensin and c-fos gene expression by typical versus atypical antipsychotics.

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Distribution of D5 dopamine receptor mRNA in rat brain

1992 • 176 citations

Subnormal CSF levels of neurotensin in a subgroup of schizophrenic patients: normalization after neuroleptic treatment

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Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites

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Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia

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Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry.

1989 • 167 citations

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1981 • 167 citations

Elevated Levels of Clozapine in Serum After Addition of Fluvoxamine

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Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

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Computed tomography of the brain in patients with acute psychosis and in healthy volunteers

1982 • 149 citations

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A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus

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Reduction of nigral glutamic acid decarboxylase in rats with neuroleptic-induced oral dyskinesia

1983 • 140 citations

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1986 • 128 citations

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1979 • 127 citations

Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene.

1991 • 125 citations

Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists

1993 • 125 citations

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1972 • 125 citations

Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells.

1991 • 124 citations

Autoradiographic localization of D1 and D2 dopamine receptors in the human brain

1988 • 124 citations

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1982 • 124 citations

Clozapine-Associated Agranulocytosis: Risk and Aetiology

1992 • 123 citations

Biochemical and behavioural properties of clozapine

1989 • 123 citations

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1989 • 122 citations

Serotonin and 5-Hydroxyindoleacetic Acid in Brains of Suicide Victims

1986 • 122 citations

Distribution of GABA in post-mortem brain tissue from control, psychotic and Huntington's chorea subjects

1980 • 118 citations

The effect of serotonergic agents on haloperidol-induced catalepsy

1990 • 118 citations

Prenatal disturbances of nerve cell migration in the entorhinal region: a common vulnerability factor in functional psychoses?

1991 • 115 citations

The dopamine hypothesis of schizophrenia: limbic interactions with serotonin and norepinephrine

1993 • 113 citations

Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatergic neuronal dysfunction

1982 • 112 citations

Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain

1990 • 112 citations

Interactions of Phencyclidine Receptor Agonist MK‐801 with Dopaminergic System: Regional Studies in the Rat

1990 • 112 citations

Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding to dopamine receptors in vivo in mouse brain

1988 • 111 citations

Chronic blockade of dopamine receptors by antischizophrenic drugs enhances GABA binding in substantia nigra

1980 • 110 citations

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1989 • 109 citations

Organization and expression of the Rat D2A receptor gene: identification of alternative transcripts and a variant donor splice site

1990 • 109 citations

High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET

1993 • 108 citations

Evidence for Different States of the Dopamine Dl Receptor: Clozapine and Fluperlapine May Preferentially Label an Adenylate Cyclase‐Coupled State of the Dl Receptor

1986 • 104 citations

Visualization of a dopamine D1 receptor mRNA in human and rat brain

1991 • 104 citations

Neurotensin modulates dopamine neurotransmission at several levels along brain dopaminergic pathways

1989 • 104 citations

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1989 • 104 citations

Turnover times of gamma-aminobutyric acid and acetylcholine in nucleus caudatus, nucleus accumbens, globus pallidus and substantia nigra: effects of repeated administration of haloperidol

1977 • 103 citations

Differential effects of antipsychotic drugs on the neurotensin concentration of discrete rat brain nuclei

1988 • 102 citations

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1989 • 102 citations

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1989 • 101 citations

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1972 • 101 citations

Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia

1993 • 100 citations

Differential expression of the mouse D2 dopamine receptor isoforms

1991 • 99 citations

Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and nucleus accumbens in vivo

1987 • 99 citations

Dopamine D1, D2 and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo.

1993 • 98 citations

Some atypical neuroleptics inhibit [3H]SCH 23390 binding in vivo

1986 • 98 citations

Clinical pharmacokinetics of clozapine in chronic schizophrenic patients

1988 • 98 citations

Chronic neuroleptic treatment enhances neurotensin receptor binding in human and rat substantia nigra

1984 • 97 citations

Effect of single and repeated administration of clozapine on the metabolism of dopamine and noradrenaline in the brain of the rat

1974 • 96 citations

Normal Ventricles in Young Schizophrenics

1982 • 94 citations

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1996 • 93 citations

Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes.

1993 • 93 citations

Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat

1985 • 93 citations

Determination of clozapine and its N-demethylated metabolite in plasma by use of gas chromatography-mass spectrometry with single ion detection

1988 • 92 citations

Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex

1989 • 91 citations

Alterations in phencyclidine and sigma binding sites in schizophrenic brains

1991 • 90 citations

Multiple-dose pharmacokinetics of clozapine in patients.

1987 • 89 citations

5-HT2 receptor blockade by ICI 169,369 and other 5-HT2 antagonists modulates the effects of D-2 dopamine receptor blockade.

1990 • 88 citations

The effects of antipsychotics on the turnover rate of GABA and acetylcholine in rat brain nuclei

1976 • 87 citations

Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia

1990 • 86 citations

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1993 • 85 citations

Biochemical pharmacology of the atypical neuroleptic remoxipride

1990 • 84 citations

In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum.

1976 • 82 citations

Increased libido in women receiving trazodone

1986 • 81 citations

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1991 • 80 citations

Analysis of the Structure and Expression of the Human Dopamine D2A Receptor Gene

1991 • 79 citations

CSF norepinephrine in schizophrenia is elevated prior to relapse after haloperidol withdrawal

1989 • 79 citations

Molecular cloning and expression of a dopamine D2 receptor from human retina.

1990 • 78 citations

Potency of antipsychotics in reversing the effects of a hallucinogenic drug on locus coeruleus neurons correlates with 5-HT2 binding affinity

1988 • 77 citations

Functional characterization of a rat dopamine D-2 receptor cDNA expressed in a mammalian cell line.

1989 • 77 citations

Cerebrospinal fluid amino acid concentrations in chronic schizophrenia

1987 • 76 citations

Motor effects of two sigma ligands mediated by nigrostriatal dopamine neurons

1989 • 75 citations

Antagonism of serotonin receptor mediated neuroendocrine and temperature responses by atypical neuroleptics in the rat

1988 • 74 citations

Brain tryptophan metabolism in schizophrenia: A post mortem study of metabolites on the serotonin and kynurenine pathways in schizophrenic and control subjects

1979 • 74 citations

Multidimensional analysis of the concentrations of 17 substances in the CSF of schizophrenics and controls

1985 • 72 citations

Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics

1991 • 71 citations

Clozapine increases rat serum prolactin levels

1975 • 71 citations

Reduced [3H]flunitrazepam binding in cingulate cortex and hippocampus of postmortem schizophrenic brains: Is selective loss of glutamatergic neurons associated with major psychoses?

1993 • 70 citations

Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists

1988 • 70 citations

Modification of the N-methyl-D-aspartate response by antidepressant σ receptor ligands

1993 • 68 citations

Clozapine is a potent and selective muscarinic antagonist at the five cloned human muscarinic acetylcholine receptors expressed in CHO-K1 cells

1991 • 68 citations

Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients.

1990 • 68 citations

Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action.

1983 • 67 citations

Impaired noradrenergic transmission in schizophrenia?

1984 • 67 citations

Electrochemistry in Vivo: Application to CNS Pharmacologya

1986 • 65 citations

Reduced CSF neurotensin concentration in drug-free schizophrenic patients

1988 • 65 citations

Serotonergic and dopaminergic aspects of neuroleptic-induced extrapyramidal syndromes in nonhuman primates

1993 • 65 citations

Clozapine has sub-micromolar affinity for 5-HT1A receptors in human brain tissue

1992 • 64 citations

The relationship between parkinsonism and tardive dyskinesia

1977 • 63 citations

BMY 14802, a Sigma Receptor Ligand for the Treatment of Schizophrenia

1994 • 63 citations

The interaction of clozapine with dopamine D1 versus dopamine D2 receptor-mediated function: behavioural indices

1990 • 62 citations

Gamma-Aminobutyric Acid (GABA) in the CSF of Schizophrenic Patients Before and After Neuroleptic Treatment

1978 • 62 citations

Differential effects of chronic treatment with haloperidol and clozapine on the level of preprosomatostatin mRNA in the striatum, nucleus accumbens, and frontal cortex of the rat

1990 • 62 citations

Haloperidol rapidly increases the number of neurotensin mRNA-expressing neurons in neostriatum of the rat brain

1991 • 62 citations

Both the σ receptor-specific ligand(+)3-PPP and the PCP receptor-specific ligand TCP act in the mouse vas deferens via augmentation of electrically evoked norepinephrine release

1987 • 61 citations

Neurotransmitter receptors in brain in schizophrenia

1981 • 61 citations

Glutamate in schizophrenics and healthy controls

1982 • 60 citations

Phencyclidine-induced ipsilateral rotation in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra

1979 • 60 citations

Model Systems For The Study Of Seven-Transmembrane-Segment Receptors

1991 • 60 citations

The effects of clozapine and fluperlapine on the in vivo release and metabolism of dopamine in the striatum and in the prefrontal cortex of freely moving rats.

1989 • 59 citations

Monoamines and monoamine metabolites in brains from demented schizophrenics

1979 • 59 citations

The effects of clozapine on shuttle-box avoidance responding in rats: Comparisons with haloperidol and chlordiazepoxide

1985 • 57 citations

(+)-6,7-Benzomorphan sigma ligands stimulate dopamine synthesis in rat corpus striatum tissue

1991 • 57 citations

The involvement of dopamine D1 and D2 receptors in the effects of the classical neuroleptic haloperidol and the atypical neuroleptic clozapine

1991 • 57 citations

Effects of halothane anaesthesia on extracellular levels of dopamine, dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid in rat striatum: a microdialysis study

1990 • 56 citations

Interaction of the atypical neuroleptic clozapine with 5-HT3 receptors in the cerebral cortex and superior cervical ganglion of the rat

1990 • 56 citations

Synergistic effects between D-1 and D-2 dopamine antagonists on catalepsy in rats

1990 • 55 citations

Locus coeruleus norepinephrine-containing neurons: effects produced by acute and subchronic treatment with antipsychotic drugs and amphetamine

1986 • 55 citations

Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of α1-noradrenergic receptors demonstrated by in vivo voltammetry

1988 • 55 citations

Anti-glutamatergic effects of clozapine

1993 • 54 citations

Stable expression of human D3 dopamine receptors in GH4C1 pituitary cells

1992 • 54 citations

Newer Antipsychotic Drugs

1993 • 51 citations

New generation of antipsychotic drugs: Novel mechanisms of action

1994 • 51 citations

Cloning of two additional catecholamine receptors from rat brain

1990 • 51 citations

Chronic haloperidol and clozapine differentially affect dynorphin peptides and substance P in basal ganglia of the rat

1986 • 51 citations

Clozapine for the treatment-resistant schizophrenic: results of a US multicenter trial

1989 • 49 citations

In vivo modulation of excitatory amino acid receptors: microdialysis studies on N-methyl-d-aspartate-evoked striatal dopamine release and effects of antagonists

1992 • 49 citations

Chronic treatment with clozapine selectively decreases basal dopamine release in nucleus accumbens but not in caudate-putamen as measured by in vivo brain microdialysis: Further evidence for depolarization block

1991 • 49 citations

Clozapine antagonism of D-1 and D-2 dopamine receptor-mediated behaviors

1989 • 47 citations

The metabolism of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e) (1,4)diazepine (clozapine) in mice, dogs and human subjects.

1971 • 47 citations

Evidence for Reduced and Dysregulated Turnover of Dopamine in Schizophrenia

1990 • 46 citations

Influence of anaesthetics on rat striatal dopamine metabolism in vivo

1986 • 46 citations

Quantitative cytoarchitectonics of the human cerebral cortex in schizophrenic dementia

1972 • 46 citations

Messenger RNA encoding the D2 dopaminergic receptor detected by in situ hybridization histochemistry in rat brain

1989 • 46 citations

Two forms of the rat D2 dopamine receptor as revealed by the polymerase chain reaction

1990 • 45 citations

Serotonin, dopamine and their interactions in schizophrenia

1993 • 45 citations

Serotonergic drugs do not substitute for clozapine in clozapine-trained rats in a two-lever drug discrimination procedure

1992 • 44 citations

The current status of PET scanning with respect to schizophrenia.

1992 • 44 citations

An early Phase II clinical trial of BW234U in the treatment of acute schizophrenia in newly admitted patients

1984 • 44 citations

Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol or thioridazine.

1994 • 44 citations

Comparison of in vitro binding properties of a series of dopamine antagonists and agonists for cloned human dopamine D2S and D2L receptors and for D2 receptors in rat striatal and mesolimbic tissues, using [125I] 2′-iodospiperone

1993 • 44 citations

Amantadine and the glutamate hypothesis of schizophrenia Experiences in the treatment of neuroleptic malignant syndrome

1993 • 44 citations

Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia

1990 • 43 citations

Effects of antipsychotic drugs on 5-HT2 receptors in the medial prefrontal cortex: microiontophoretic studies

1990 • 43 citations

Noncompetitive N-methyl-D-aspartate antagonists affect multiple ionic currents.

1988 • 42 citations

The Mouse Dopamine D2A Receptor Gene: Sequence Homology with the Rat and Human Genes and Expression of Alternative Transcripts

1991 • 41 citations

Presynaptic regulation of electrically evoked dopamine overflow in nucleus accumbens: a pharmacological study using fast cyclic voltammetry in vitro

1991 • 41 citations

Brain monoamine changes in chronic paranoid schizophrenia and their possible relation to increased dopamine receptor sensitivity.

1980 • 41 citations

Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats

1990 • 40 citations

Similarity of clozapine and SCH 23390 in reserpinized rats suggests a common mechanism of action

1987 • 39 citations

Basic biology of clozapine: electrophysiological and neuroendocrinological studies

1989 • 39 citations

The Neurobiology of Schizophrenia

2016 • 38 citations

Haloperidol but Not Clozapine Increases Neurotensin Receptor mRNA Levels in Rat Substantia Nigra

1993 • 38 citations

Effects of acute and chronic clozapine and haloperidol on in vitro release of acetylcholine and dopamine from striatum and nucleus accumbens.

1989 • 38 citations

Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat

1987 • 36 citations

The Scottish First Episode Schizophrenia Study

1989 • 36 citations

Computerised Tomography in Newly Diagnosed Schizophrenia and Schizophreniform Disorder

1993 • 36 citations

Sigma receptor "antagonist" BMY 14802 increases neurotensin concentrations in the rat nucleus accumbens and caudate.

1990 • 36 citations

Dopamine D4 receptors: curiouser and curiouser

1994 • 35 citations

Age-related variations in relative abundance of alternative spliced D2 receptor mRNAs in brain areas of two rat strains

1992 • 34 citations

Chronic fluphenazine and clozapine elicit opposite changes in brain muscarinic receptor binding: implications for understanding tardive dyskinesia.

1983 • 33 citations

Chronic clozapine treatment decreases 5-hydroxytryptamine1C receptor density in the rat choroid plexus: comparison with haloperidol.

1993 • 32 citations

Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy

1975 • 32 citations

Potency mismatch for behavioral and biochemical effects by dopamine receptor antagonists: implications for the mechanism of action of clozapine

1993 • 31 citations

Hypothalamic infusion of the 5-HT21C agonist, DOI, prevents the inhibitory actions of the 5-HT1A agonist, 8-OH-DPAT, on lordosis behavior

1994 • 30 citations

Acute administration of clozapine, thioridazine and metoclopramide increases extracellular DOPAC and decreases extracellular 5-HIAA, measured in the nucleus accumbens and striatum of the rat using in vivo voltammetry

1987 • 28 citations

Identification by sequence analysis of a second rat brain cDNA encoding the dopamine (D2) receptor

1990 • 28 citations

Non‐equilibrium Method for the Radioimmunoassay of Clozapine in the Presence of Metabolites

1977 • 27 citations

Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines

1976 • 27 citations

A contribution to the morphological background of schizophrenia

1964 • 26 citations

Selection of control populations for clinical cerebrospinal fluid GABA investigations based on comparison with normal volunteers

1980 • 26 citations

3H-spiroperidol binding to dopamine receptors in rat striatal membranes: Influence of loxapine and its hydroxylated metabolites

1979 • 26 citations

GABAergic supersensitivity within the pars reticulata of the rat substantia nigra following chronic haloperidol administration

1987 • 26 citations

Hippocampal benzodiazepine receptors in schizophrenia

1993 • 24 citations

Chronic clozapine treatment down-regulates serotonin 5-HT-1c receptors in rat brain

1992 • 24 citations

Chronicles in drug discovery

2010 • 24 citations

Effects of acute and chronic clozapine on dopaminergic function in medial prefrontal cortex of awake, freely moving rats

1992 • 23 citations

Differences in lateral brain ventricular size among various types of chronic schizophrenics: EVIDENCE BASED ON A CT STUDY

1982 • 23 citations

Synergistic blockade of some dopamine-mediated behaviours by (?)-sulpiride and SCH 23390 in the rat

1989 • 23 citations

Pharmacology of Fluperlapine Compared with Clozapin

1985 • 23 citations

Does treatment with haloperidol for 3 weeks produce depolarization block in midbrain dopamine neurons of unanaesthetized rats?

1988 • 22 citations

A mechanism for the involvement of colocalized neuropeptides in the actions of antipsychotic drugs

1989 • 21 citations

Increased grooming behaviour is induced by apomorphine in mice treated with discriminant benzamide derivatives

1988 • 21 citations

Acute effects of Sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons

1992 • 21 citations

New pharmacological approaches to the therapy of depressive disorders

1995 • 21 citations

5-HT1C receptor-mediated phosphoinositide hydrolysis in the rat choroid plexus after chronic treatment with clozapine

1994 • 20 citations

Multiple neurochemical action of clozapine: A quantitative autoradiographic study of DA 2, opiate and benzodiazepine receptors in the rat brain after long-term treatment

1991 • 20 citations

Differential effects of the stereoisomers of 3PPP in dopaminergic and cholinergic neurotransmission in superfused slices of the corpus striatum

1984 • 19 citations

The effect of clozapine on prolactin secretion at the level of the lactotroph

1990 • 18 citations

Concurrent treatment with benztropine and haloperidol attenuates development of behavioral hypersensitivity but not dopamine receptor proliferation

1988 • 17 citations

Effects of the optical isomers of the narcotic antagonist analgesic pentazocine on brain and heart biogenic amines

1974 • 15 citations

The Psychobiology of Neurotensin

1988 • 15 citations

Antagonism of AP-5- and amphetamine-induced behaviour by timelotem as compared with clozapine and haloperidol

1987 • 15 citations

Neuroleptic piperazinyl-dibenzo-azepines. Chemistry and structure-activity relationships.

1975 • 14 citations

Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat

1993 • 14 citations

Antagonism of AP-5-induced sniffing stereotypy links umespirone to atypical antipsychotics

1991 • 14 citations

Effects of CI‐943, a potential antipsychotic drug, and haloperidol on regional brain neurotensin concentrations

1991 • 13 citations

History of Psychopharmacology

2014 • 13 citations

Lack of involvement of haloperidol-sensitive sigma binding sites in modulation of dopamine neuronal activity and induction of dystonias by antipsychotic drugs

1992 • 13 citations

[3H]dopamine binds to D-1 and D-2 receptors in rat striatum

1983 • 13 citations

Long-term treatment with antipsychotics does not alter the phosphoinositide response to muscarinic or D2 dopaminergic agonists in rat striatum

1989 • 12 citations

[Neurobiology of schizophrenia].

1993 • 12 citations

A long‐term study of remoxipride in chronic schizophrenic patients

1993 • 12 citations

The effect of chronic clozapine on basal dopamine release and apomorphine-induced DA release in the striatum and nucleus accumbens as measured by in vivo brain microdialysis

1992 • 11 citations

Determination of N‐Acetylaspartic Acid in Human Cerebrospinal Fluid by Gas Chromatography–Mass Spectrometry

1990 • 11 citations

[3H]Nipecotic Acid Binding to γ‐Aminobutyric Acid Uptake Sites in Postmortem Human Brain

1990 • 11 citations

Clozapine fails to prevent the development of haloperidol-induced behavioral hypersensitivity in a cotreatment paradigm

1990 • 9 citations

Biochemical pharmacology of the atypical neuroleptic remoxipride

1991 • 9 citations

Further characterization of the effects of BMY 14802 on dopamine neuronal activity

1993 • 8 citations

Striatal Dopamine Releasea: In Vivo Evidence for Local Initiation

1990 • 7 citations

Pharmacological Effects of Zotepine and other Antipsychotics on the Central 5-HT2Receptors

1993 • 7 citations

Enhancement of the in vivo binding of [3h]flunitrazepam by the atypical neuroleptic, clozapine

1987 • 7 citations

A comparative study of neurotensin inactivation by brain peptidases from different vertebrate species

1984 • 6 citations

The effect of serotonergic agents on haloperidol-induced catalepsy

1989 • 4 citations

Selection of control populations for clinical cerebrospinal fluid GABA investigations based on comparison with normal volunteers

1979 • 3 citations

Signalling via rat dopamine D2-receptors expressed in mouse fibroblasts is not influenced by compounds binding to the sigma sites of these cells

1993 • 3 citations

Deleted Work

1955 • 0 citations

Cited By (0)

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New Insights into the Biology of Schizophrenia through the Mechanism of Action of… (1995) – Neuropsychopharmacology | Metascience Observatory Explorer