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

  title={Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding},
  author={Alain Schotte and Paul F. M. Janssen and Walter Gommeren and Walter Luyten and Paul T. Van Gompel and Anne Simone Josephine Lesage and K. De Loore and Jos{\'e}e E. Leysen},
Risperidone and its active metabolite 9-OH-risperidone were compared to reference antipsychotic drugs (haloperidol, pipamperone, fluspirilene, clozapine, zotepine) and compounds under development (olanzapine, seroquel, sertindole, ORG-5222, ziprasidone) for in vitro binding to neurotransmitter receptors in brain tissue and on membranes of recombinant cells expressing cloned human receptors and for in vivo occupancy of neurotransmitter receptors in rat and guinea-pig brain following acute… 

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 clozAPine, as well as its central and peripheral side effects such as sedation and weight gain.

Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

Comparison of D2R occupancy and serum drug levels supports a target of 40 to 80 ng/ml active drug for these two atypical antipsychotics.

Central Muscarinic Acetylcholine Receptor Availability in Patients Treated with Clozapine

Preliminary data indicate that reduction of mus carinic receptor availability by clozapine can be measured in vivo and that moderate daily doses are associated with moderate to high reductions of muscarinic receptors availability.

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.

The Pharmacological Role and Clinical Applications of Antipsychotics' Active Metabolites: Paliperidone versus Risperidone

The pharmacological differences between risperidone and paliperidone could explain the differential clinical response exhibited by schizophrenic patients treated with both agents, as well as some differences in tolerability profile and drug interactions.

Comparison of the in-vivo muscarinic cholinergic receptor availability in patients treated with clozapine and olanzapine.

  • T. Raedler
  • Psychology, Medicine
    The international journal of neuropsychopharmacology
  • 2007
The results suggest that treatment with clozapine results in a stronger blockade of the muscarinic cholinergic receptors than with olanzapine, compatible with the higher rates of anticholinergic side-effects seen with clazapine in clinical practice.

N-Desmethylclozapine, a Major Metabolite of Clozapine, Increases Cortical Acetylcholine and Dopamine Release In Vivo Via Stimulation of M1 Muscarinic Receptors

NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.

Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics.

Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors.



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.

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.

Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity and dopamine release selectively in the mesolimbic dopaminergic system

Findings provide an experimental basis for the notion that combined 5-HT2 and D2 receptor antagonism may underlie the limbic mode of action of at least some atypical antipsychotic drugs and consequently contribute to their unique therapeutic effects.

Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine

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.

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.

Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4.

  • P. Seeman
  • Psychology, Medicine
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1992
An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.

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.

Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.

The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 and rat5-HT7 receptors in transiently expressed COS-7 cells or stably transfected HEK-293 cells to identify those with high affinity for the newly discovered 5-HT6 receptor.