Asenapine: a novel psychopharmacologic agent with a unique human receptor signature

  title={Asenapine: a novel psychopharmacologic agent with a unique human receptor signature},
  author={Mohammed Shahid and GB Walker and SH Zorn and Ehf Wong},
  journal={Journal of Psychopharmacology},
  pages={65 - 73}
Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pK i) for serotonin receptors… 

Figures and Tables from this paper

Asenapine induces differential regional effects on serotonin receptor subtypes
It is indicated that repeated administration of asenapine produces regional-specific effects on 5-HT1A and 5- HT2A receptors in rat forebrain regions, which may contribute to the distinctive psychopharmacologic profile of asENapine.
Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia
Its ability to increase both dopaminergic and glutamatergic activity in rat mPFC suggests that asenapine may possess an advantageous effect not only on positive symptoms in patients with schizophrenia, but also on negative and cognitive symptoms.
Serotonergic mechanisms as targets for existing and novel antipsychotics.
  • H. Meltzer
  • Psychology, Biology
    Handbook of experimental pharmacology
  • 2012
An update of current preclinical and clinical evidence for the role of these five 5-HT receptors in the actions of current APDs and for the development of novel psychotropic drugs is provided.
Cariprazine (RGH-188), a Dopamine D3 Receptor-Preferring, D3/D2 Dopamine Receptor Antagonist–Partial Agonist Antipsychotic Candidate: In Vitro and Neurochemical Profile
The antagonist–partial agonist properties of cariprazine at D3 and D2 receptors, with very high and preferential affinity to D3 receptors, make it a candidate antipsychotic with a unique pharmacological profile among known antipsychotics.
Differential regional and dose-related effects of asenapine on dopamine receptor subtypes
Results indicate that asenapine has region-specific and dose-dependent effects on dopamine receptor subtypes in rat forebrain, which may contribute to asenAPine’s unique psychopharmacological properties.
Evaluation of the clinical efficacy of asenapine in schizophrenia
Asenapine is a recently approved agent with an acceptable cardiometabolic profile and exhibits similar efficacy as other antipsychotic medications, primarily on positive symptoms of schizophrenia.
Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism
  • L. Citrome
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2014
This review describes the chemistry, pharmacodynamics, and pharmacokinetics of asenapine, a second-generation antipsychotic currently marketed for the treatment of schizophrenia and bipolar mania/mixed episodes that has a complex pharmacodynamic profile with affinities at multiple dopamine, serotonin, histamine, and α-adrenergic receptors.
The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania
This review analyzes the pharmacological, neurochemical, behavioral, and molecular mechanisms of asenapine and their contribution to the beneficial therapeutic advantages of the drug as reported in published preclinical and clinical studies, product labels, and poster presentations.
Receptor mechanisms of antipsychotic drug action in bipolar disorder – focus on asenapine
  • G. Reynolds
  • Psychology, Medicine
    Therapeutic advances in psychopharmacology
  • 2011
The relative benefits of atypical antipsychotics like asenapine can be understood from their receptor pharmacology, and this understanding is key to the future development of improved treatment for bipolar disorder.
5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482].


Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology
The results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of ‘functionally selective’ activation of D2 (and possibly D3)-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors—particularly 5-HT receptor subtypes (5-HT1A, 5- HT2A).
Serotonin receptors : their key role in drugs to treat schizophrenia
5-ht6 receptors.
All aspects of the discovery, genetics, distribution, pharmacology and function of the 5-ht(6) receptor, which appears to regulate glutamatergic and cholinergic neuronal activity, warrants the use of the upper case nomenclature.
Serotonergic basis of antipsychotic drug effects in schizophrenia
Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders
Evidence is provided for and against the use of selective 5-HT receptor drugs as cognition enhancing agents for schizophrenia and other disorders, and it is likely that serotonergic drugs will soon be available as cognition enhances medications for disorders other than schizophrenia.
A Comparative Review of New Antipsychotics
  • O. Blin
  • Psychology, Medicine
    Canadian journal of psychiatry. Revue canadienne de psychiatrie
  • 1999
A decision algorithm for comparing drugs used for psychotic disorders, based on biochemical profile, experimental pharmacology, postiron emission tomography (PET) scan results, and clinical efficacy on positive, negative, anxious, depressive, and cognitive symptoms is proposed.
α-Adrenoceptor modulation hypothesis of antipsychotic atypicality
  • T. Svensson
  • Psychology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2003
Pharmacogenetic studies of response to risperidone and other newer atypical antipsychotics.
Although investigators have started to explore genetic effects on cognitions of schizophrenia patients receiving antipsychotics, future larger sized pharmacogenetic studies on both psychotic symptoms and cognitive functions are warranted.