Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography

  title={Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography},
  author={Alain Schotte and Paul F. M. Janssen and Anton A Megens and Jos{\'e}e E. Leysen},
  journal={Brain Research},

Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding

Risperidone and its active metabolite 9-OH-risperidone were compared to reference antipsychotic drugs (haloperidol, pipamperone, fluspirilene, clozapine, zotepine) and compounds under development

Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain

In contrast to the regionally rather homogenous activation of brain DA systems caused by risperidone, the drug was found to enhance brain 5-HT metabolism preferentially in the MPC, as indicated by the elevated extracellular concentration of 5-HIAA in this region.

Survey on the pharmacodynamics of the new antipsychotic risperidone

Risperidone can be characterized as a potent D2 antagonist with predominant 5HT2 antagonistic activity and optimal pharmacokinetic properties.

In vitro receptor binding and in vivo receptor occupancy in rat and guinea pig brain: risperidone compared with antipsychotics hitherto used.

The predominant 5-HT2A-receptor occupancy most likely underlies risperidone's beneficial effects on the negative symptoms of schizophrenia and an adequately low D2-receptors occupancy adds to the treatment of positive symptoms with a low liability of EPS.

Selective effects on prefrontal cortex serotonin by dopamine D3 receptor agonism: Interaction with low-dose haloperidol

  • M. R. Lynch
  • Psychology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 1997

Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo

Clozapine and its active metabolite NDMC interact with the four human histamine receptors at clinically relevant concentrations, which may substantiate, at least in part, the atypical antipsychotic profile of clozapines, as well as its central and peripheral side effects such as sedation and weight gain.



In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone.

In vivo binding in rats, using intravenous administration of [3H]spiperone, and in vitro receptor binding and monoamine uptake inhibition profiles, revealed very potent occupation by ocaperidone and risperidone of 5HT2 receptors in the frontal cortex, which were 6, 30, and 100 times more potent than ritanserin, haloperidol, and clozapine.

Biochemical profile of risperidone, a new antipsychotic.

Risperidone enhanced at nanomolar concentrations the stimulated [3H]norepinephrine efflux from cortical slices and it similarly reversed the inhibition by clonidine, at concentrations corresponding to its binding affinity for alpha-2 adrenergic receptors.

Pharmacology of risperidone (R 64 766), a new antipsychotic with serotonin-S2 and dopamine-D2 antagonistic properties.

The first clinical studies indicate that two additional therapeutic targets may be obtained with risperidone in the monotherapy of schizophrenia and related disorders: very important contact and mood-elevating properties and extrapyramidal symptoms-free maintenance therapy.

The nucleus accumbens–possible site of antipsychotic action of neuroleptic drugs?

Results are consistent with the hypothesis that these drugs exert their therapeutic effects by dopamine receptor blockade in the nucleus accumbens, and are in the rank order in which these drugs produce extrapyramidal side effects.

Differential sensitivity of two dopaminergic structures in rat brain to haloperidol and to clozapine.

The mechanisms underlying the dissociation of the extrapyramidal and antipsychotic properties of haloperidol as compared to clozapine were explored by studying the effects of these drugs on dopamine

5-HT2 antagonist ritanserin in neuroleptic-induced parkinsonism: a double-blind comparison with orphenadrine and placebo.

The results confirm previous observations of the therapeutic efficacy of ritanserin on neuroleptic-induced parkinsonism, and support the hypothesis that serotonin influences extrapyramidal physiopathology.

In vitro and in vivo binding characteristics of a new long-acting histamine H1 antagonist, astemizole.

The most striking property of this drug is its extremely slow dissociation rate from H1 receptors when assayed in vitro using [3H]-pyrilamine, and here again the most striking receptor binding property was its very long duration.

Neuroleptic affinities for human brain receptors and their use in predicting adverse effects.

  • E. Richelson
  • Medicine, Biology
    The Journal of clinical psychiatry
  • 1984
Differences in affinities allow the clinician to choose drugs with low affinity for certain receptors and, thereby, minimize some of the adverse effects of these drugs in patients.

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

The blockade of D-2 receptors by haloperidol results in a compensatory increase in rat striatal DA metabolism, which is enhanced by ICI 169,369, and data suggest that the 5-HT2 component of these compounds, by enhancingDA metabolism, may act to attenuate the blockade of striatal D- 2 receptors by these compounds.