Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences

@article{Aringhieri2018MolecularTO,
  title={Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences},
  author={Stefano Aringhieri and Marco Carli and Shivakumar Kolachalam and Valeria Verdesca and Enrico Cini and Mario Rossi and Peter J. McCormick and Giovanni Umberto Corsini and Roberto Maggio and Marco Scarselli},
  journal={Pharmacology \& Therapeutics},
  year={2018},
  volume={192},
  pages={20–41}
}

Figures and Tables from this paper

Antipsychotic Drug Development: From Historical Evidence to Fresh Perspectives
TLDR
Improving the lives of sub-populations of people with schizophrenia that share common biological characteristics and are likely to be responsive to a particular compound may be more achievable than aiming to treat the complexities of schizophrenia as a homogenous disorder.
Regulation of Glutamatergic Activity via Bidirectional Activation of Two Select Receptors as a Novel Approach in Antipsychotic Drug Discovery
TLDR
The present review summarizes the results of the latest papers, showing that the simultaneous activation of two receptors with sub-effective doses of their ligands induces similar effects as the highest dose of each compound alone.
Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics
TLDR
The progresses made in the identification of allosteric drugs for dopamine and serotonin receptors are summarized, which could lead to a new generation of atypical antipsychotics with a better profile, especially in terms of reduced side effects.
Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856
TLDR
Intermediate-early genes expression was strongly upregulated in the prefrontal cortex and, to a less extent, in the ventral hippocampus, suggesting an activation of these regions, suggesting that modulation of the PFC may represent an important mechanism for the functional and behavioural activity of this novel compound.
Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics
TLDR
This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.
Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity
TLDR
Findings show that chronic exposure to blonanserin modulates selective IEGs with a specific anatomical profile, and the differential activation of specific brain regions under challenging conditions may contribute to specific clinical features of the drug.
Anti-stress Properties of Atypical Antipsychotics
TLDR
Examination of existing clinical and preclinical evidence that supports the ability of atypical antipsychotic drugs (AAPDs) to modulate stress-related alterations discusses stress- related mechanisms, spanning from neuroendocrine function to inflammation and neuronal plasticity, which are relevant for the manifestation of schizophrenic symptomatology.
Clozapine and Constipation: A Review of Clinical Considerations and Treatment Options
TLDR
Constipation is an often overlooked, common side effect that can limit clozapine’s use and can also be life-threatening, especially when considering the strong anticholinergic effects of clozAPine.
The Effect of Atypical Anti-psychotic Agents on Obesity and Glucose Metabolism
TLDR
The mechanisms of hyperglycemia and hypoglycemia were mainly related obesity, decreased anorexigenic hormones, and increased insulin resistance in multiple organs, and these are frequently reported in Asians.
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences
TLDR
There seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations, and a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS.
...
...

References

SHOWING 1-10 OF 366 REFERENCES
Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents
TLDR
An update and critical review of the pharmacology and clinical profiles of current antipsychotic drugs and drugs acting on novel targets with potential to be therapeutic agents in the future is provided.
Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs
TLDR
A brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotic drugs is provided, and focuses on novel targets for therapeutic agents for future drug development.
Update on typical and atypical antipsychotic drugs.
  • H. Meltzer
  • Psychology, Medicine
    Annual review of medicine
  • 2013
TLDR
Overall, choosing among the atypical APDs as first-line treatment represents the best course for schizophrenia and most likely other disorders for which APDs are used.
The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives.
TLDR
The balance of 5-HT1A/D2 receptor properties should be considered when selecting compounds as antipsychotic development candidates and such differences are likely to translate into distinct therapeutic profiles.
Antipsychotic drug actions on gene modulation and signaling mechanisms.
Pharmacogenetics as a tool in the therapy of schizophrenia
AbstractAim: This review summarises the present knowledge of associations between pharmacogenetics and therapeutic efficacy and side effects of antipsychotics to enable pharmacists to judge the
α-Adrenoceptor modulation hypothesis of antipsychotic atypicality
  • T. Svensson
  • Psychology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2003
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
TLDR
It is demonstrated that both typical and atypical antipsychotic drugs may exhibit inverse agonist effects at the 5- HT2C-INI isoform of the human 5-HT2C receptor and that no relationship exists between inverse agonists actions and attypicality.
Molecular mechanisms underlying synergistic effects of SSRI–antipsychotic augmentation in treatment of negative symptoms in schizophrenia
TLDR
While as yet limited in scope, the evidence suggests definable molecular targets which may be implicated in drug development based on SSRI–antipsychotic synergistic actions.
...
...