Biochemical pharmacology of the atypical neuroleptic remoxipride

@article{Khler1990BiochemicalPO,
  title={Biochemical pharmacology of the atypical neuroleptic remoxipride},
  author={Christer K{\"o}hler and H{\aa}kan Hall and Olle Magnusson and Tommy Lewander and Kristin Gustafsson},
  journal={Acta Psychiatrica Scandinavica},
  year={1990},
  volume={82}
}
Abstract In vitro receptor ligand binding studies in the rat showed that remoxipride displaced different radioligands at the dopamine D2, but not the D1 receptor. Remoxipride did not block dopamine‐stimulated adenylate cyclase activity in vitro suggesting that it did not directly interact with the dopamine D1 receptor. Like other antipsychotic compounds, it increased dopamine turnover in the dopamine‐rich areas of the brain. It showed no affinity for a wide range of neurotransmitter receptors… 
Effects of remoxipride's metabolites on dopamine D2 receptors and receptor functions in the rat.
TLDR
Analysis of the effectiveness of the DA receptor blockade after intraperitoneal or subcutaneous administration suggested that FLA 797 (-)/FLA 908 (-) may only contribute marginally to the D2 receptor-blocking activity of remoxipride in the rat, and the weak DA D2 blocking effect of the pyrrolidone metabolites indicated that remxipride is responsible for the clinical action.
Distribution of remoxipride to the human brain and central D2‐ dopamine receptor binding examined in vivo by PET
  • L. Farde, C. Bahr
  • Chemistry, Medicine
    Acta psychiatrica Scandinavica. Supplementum
  • 1990
TLDR
Positron emission tomography and the ligand [C] raclopride were used to examine the central D2‐dopamine receptor occupancy in man during oral administration of remoxipride and found occupancy values were similar to the values previously found in a series of patients treated with neuroleptics representative of all currently used chemical classes.
Pharmacology of the atypical antipsychotic remoxipride, a dopamine D2 receptor antagonist.
TLDR
In animals, remoxipride has minimal cataleptic effects at doses that block dopamine agonist-induced hyperactivity and these findings are predictive of antipsychotic activity with a low likelihood of extrapyramidal symptoms.
Remoxipride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in schizophrenia.
TLDR
Clinical data show that remoxipride has antipsychotic acticvity in patients with chronic schizophrenia, and acute exacerbation of Chronic schizophrenia, with activity on both positive and negative symptoms, and it appears to offer an important tolerability advantage over haloperidol.
Does the dopamine receptor subtype selectivity of antipsychotic agents provide useful leads for the development of novel therapeutic agents?
TLDR
The receptor-binding profiles of a series of antipsychotic agents are studied and some of the compounds in behavioural assays in the rat are evaluated and speculations on the key-target of clinically interesting antipsychotics (including clozapine) may be of little practical value.
The role of dopamine, 5-hydroxytryptamine, sigma and NMDA receptors in the action of antipsychotic drugs
TLDR
Several studies suggest a significant functional connection of PCP and sigma receptors with the mesolimbic and cort­ ical dopaminergic neurones in rats, and Rimcazole and BMY 14802 were shown to be relatively selective ligands at sigma binding sites in CNS tissues with no ap­ preciable affinity for dopamine receptors.
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References

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Distribution of remoxipride to the human brain and central D2‐ dopamine receptor binding examined in vivo by PET
  • L. Farde, C. Bahr
  • Chemistry, Medicine
    Acta psychiatrica Scandinavica. Supplementum
  • 1990
TLDR
Positron emission tomography and the ligand [C] raclopride were used to examine the central D2‐dopamine receptor occupancy in man during oral administration of remoxipride and found occupancy values were similar to the values previously found in a series of patients treated with neuroleptics representative of all currently used chemical classes.
Effects of remoxipride and some related new substituted salicylamides on rat brain receptors.
A number of potential neuroleptic drugs of the substituted benzamide type have been compared with some reference neuroleptic drugs regarding their affinities for rat brain receptors using in vitro
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TLDR
The results suggest that remoxipride, unlike haloperidol, can discriminate between different types of dopamine mediated functions probably by having a preferential action on subpopulations of functionally coupled dopamine D2 receptors.
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TLDR
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TLDR
Tolerance to the effects of repeated haloperidol treatment on dopamine turnover was observed as soon as after 3 days, whereas no such tolerance could be found during the first 15 days of repeated treatment with remoxipride.
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