Antipsychotics: mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "Antipsychotics: mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology."

Antipsychotic drugs are central to the treatment of schizophrenia and other psychotic disorders but are ineffective for some patients and associated with side-effects and nonadherence in others. We review the in vitro, pre-clinical, clinical and molecular imaging evidence on the mode of action of antipsychotics and their side-effects. This identifies the key role of striatal dopamine D2 receptor blockade for clinical response, but also for endocrine and motor side-effects, indicating a therapeutic window for D2 blockade. We consider how partial D2/3 receptor agonists fit within this framework, and the role of off-target effects of antipsychotics, particularly at serotonergic, histaminergic, cholinergic, and adrenergic receptors for efficacy and side-effects such as weight gain, sedation and dysphoria. We review the neurobiology of schizophrenia relevant to the mode of action of antipsychotics, and for the identification of new treatment targets. This shows elevated striatal dopamine synthesis and release capacity in dorsal regions of the striatum underlies the positive symptoms of psychosis and suggests reduced dopamine release in cortical regions contributes to cognitive and negative symptoms. Current drugs act downstream of the major dopamine abnormalities in schizophrenia, and potentially worsen cortical dopamine function. We consider new approaches including targeting dopamine synthesis and storage, autoreceptors, and trace amine receptors, and the cannabinoid, muscarinic, GABAergic and glutamatergic regulation of dopamine neurons, as well as post-synaptic modulation through phosphodiesterase inhibitors. Finally, we consider treatments for cognitive and negative symptoms such dopamine agonists, nicotinic agents and AMPA modulators before discussing immunological approaches which may be disease modifying.


Journal Details

This article was published in the following journal.

Name: Neuropharmacology
ISSN: 1873-7064
Pages: 107704


DeepDyve research library

PubMed Articles [47658 Associated PubMed Articles listed on BioPortfolio]

Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics: Results From the National FACE-SZ Cohort.

Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical tri...

Inhibition of Recombinant Human Acetylcholinesterase Activity by Antipsychotics.

Extrapyramidal symptoms (EPS) are representative side effects of antipsychotics, caused by their inhibitory action on dopaminergic nerves in nigrostriatal pathways. EPS could be also caused by direct ...

Solving the Opioid Crisis: Respiratory Depression by Opioids as Critical Endpoint.

Opioid overdose is due to misuse of prescription pain killers such as oxycodone, as well as misuse of street drugs like heroin or fentanyl. Opioid overdoses are responsible for the deaths of over 50,0...

Reasons for clozapine discontinuation in patients with treatment-resistant schizophrenia.

Although clozapine is more effective than other antipsychotics in the treatment of schizophrenia, the rate of its discontinuation is also high. The aim of this retrospective chart-review study was to ...

Aripiprazole overdose and transient 2:1 second degree atrioventricular block: only a coincidence?

Atypical antipsychotics, unlike traditional antipsychotics, are considered to have limited cardiovascular side effects, but recent evidence drew attention to potential cardiac rhythm disturbances duri...

Clinical Trials [16045 Associated Clinical Trials listed on BioPortfolio]

Identifying Predictors of Response to Antipsychotics Using a Treatment Algorithm

The objective of this study is to evaluate predictors of response to antipsychotic medication in subjects with schizophrenia. The investigators will evaluate psychopathology,brain MRI, gen...

Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis

The benefits and harms of antipsychotics are relatively well studied in adults. However, there is a lack of scientifically valid studies regarding the benefits and harms of antipsychotics ...

A Pharmacogenetic Investigation of Antipsychotics in Schizophrenia and Schizophrenia-Like Psychoses

An individual's genetic make-up is known to determine their response to antipsychotic medication. Genetic markers that determine efficacy and side effects of medication may be identified a...

Side Effects of Newer Antipsychotics in Older Adults

This study will compare four atypical antipsychotic medications in terms of the risk of specific side effects each of them presents in middle-aged and elderly individuals.

Efficacy and Tolerability of Switching to Ziprasidone From Other Antipsychotics

Because ziprasidone has not been extensively studied and is not widely accepted in the severely mentally ill in State hospitals this study aims to demonstrate its effectiveness and relativ...

Medical and Biotech [MESH] Definitions

The observable response made to a situation and the unconscious processes underlying it.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

A thioxanthine with effects similar to the phenothiazine antipsychotics.

A thioxanthine used as an antipsychotic agent. Its effects are similar to the phenothiazine antipsychotics.

A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)

Quick Search


DeepDyve research library

Relevant Topics

Schizophrenia is a common  serious long-term mental health condition that affects 5 in 1000 in the UK. It causes a range of different psychological symptoms; hallucinations, delusions, muddled thoughts based on the hallucinations or delusions and ch...

Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake.  Diagnosis is based on clinical presentation...

Searches Linking to this Article