Is amoxapine an atypical antipsychotic? positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy

@article{Kapur1999IsAA,
  title={Is amoxapine an atypical antipsychotic? positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy},
  author={Shitij Kapur and Raymond Cho and Corey Jones and Gordon Mckay and Robert B Zipursky},
  journal={Biological Psychiatry},
  year={1999},
  volume={45},
  pages={1217-1220}
}
Addition of amoxapine improves positive and negative symptoms in a patient with schizophrenia
TLDR
The improvement, following amoxapine initiation, of positive and negative symptoms in a patient with schizophrenia who had shown lack of clinical response to a robust antipsychotic regimen is reported.
Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study.
TLDR
During treatment with clinical doses of paroxetine or citalopram, approximately 80% of 5-HTT receptors are occupied, which is greater than the known physiological range of changes in 5- HTT binding potential but may be necessary for some therapeutic effects.
Amoxapine as an Antipsychotic: Comparative Study Versus Haloperidol
TLDR
Amoxapine may be as effective an antipsychotic as haloperidol as predicted by its affinity for D2 and 5HT2 receptors, supporting earlier studies, but it did not prove to have fewer extrapyramidal side effects than hal operidol, possibly because the baseline scores were very low.
In Vivo Occupancy of Dopamine D3 Receptors by Antagonists Produces Neurochemical and Behavioral Effects of Potential Relevance to Attention-Deficit–Hyperactivity Disorder
TLDR
The present findings indicate that dopamine D3 receptor antagonists engender cognition-enhancing and hyperactivity-dampening effects and could be considered as a novel treatment approach for cognitive deficits andhyperactivity syndromes, including those observed in ADHD.
Amoxapine as an Atypical Antipsychotic: A Comparative Study Vs Risperidone
TLDR
Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotic drugs, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics.
Reply: Atypical Antipsychotics Mechanisms of Action
TLDR
The observation that olanzapine treatment, which PD patients tolerate poorly owing to motor dysfunction, is virtually free from acute dystonic reactions—a property shared by quetiapine and clozapine, but not by risperidone is intriguing.
Reply: Atypical Antipsychotics Mechanisms of Action
TLDR
The observation that olanzapine treatment, which PD patients tolerate poorly owing to motor dysfunction, is virtually free from acute dystonic reactions—a property shared by quetiapine and clozapine, but not by risperidone is intriguing.
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References

SHOWING 1-10 OF 19 REFERENCES
5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation.
TLDR
Olanzapine is a potent 5- HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses, however, its D1 occupancy is higher than that of clozapine and similar to that of risperidone.
PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophrenia.
TLDR
Loxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy, but it is not "atypical" like clozapine and risperidone, since its 5- HT2 occupancy is not higher than its D2 occupancy.
A new framework for investigating antipsychotic action in humans: lessons from PET imaging
  • S. Kapur
  • Psychology, Medicine
    Molecular Psychiatry
  • 1998
TLDR
A framework is suggested wherein antipsychotics may be classified on the basis of their D2 and 5-HT2 occupancy in patients at steady state while taking clinically relevant doses, and the justification, limitations and the value of this framework in understanding and investigating newer antipsychotic is discussed.
D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.
TLDR
The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extrapyramidal side effects.
The Role of Serotonin in Schizophrenia and the Place of Serotonin‐Dopamine Antagonist Antipsychotics
  • H. Meltzer
  • Psychology, Medicine
    Journal of clinical psychopharmacology
  • 1995
TLDR
The serotonin‐dopamine antagonists may prove to have many other uses in psychiatry beyond schizophrenia because of their low propensity to cause extrapyramidal symptoms and their pharmacologic mechanism of action may be more complex than only strong 5‐HT2A and weak D2 block.
The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent.
TLDR
It is predicted that olanzapine will have an atypical profile and will be less likely to induce undesirable extrapyramidal symptoms than currently available drugs.
Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.
The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding
A Method for the In Vivo Investigation of the Serotonergic 5‐HT2 Receptors in the Human Cerebral Cortex Using Positron Emission Tomography and 18F‐Labeled Setoperone
TLDR
These data in humans with PET demonstrate that [18F]setoperone labels with high sensitivity and selectivity 5‐HT2 receptors in the frontal cortex are binding to plasma proteins and is significantly metabolized into several labeled metabolites that are much more hydrophilic than setoperone and, hence, presumably do not cross the blood–brain barrier.
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