Novel Approaches for Treating Psychotic Disorders

2017 ◽  
Author(s):  
Tiago Reis Marques ◽  
Shitij Kapur
Keyword(s):  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
D2 Receptor ◽  
Cognitive Remediation ◽  
Mechanisms Of Action ◽  
Serotoninergic System ◽  
Antipsychotic Medications ◽  
Alpha7 Nicotinic Acetylcholine Receptor ◽  
New Treatments

Current antipsychotic medications have been the mainstay in the treatment of schizophrenia since chlorpromazine was introduced in 1952. However, all antipsychotics share the same mechanism of action, which involves a blockade of the dopamine D2-receptor. This chapter covers recent attempts to develop new treatments for psychotic disorders. These include new approaches to the delivery of existing antipsychotic medications and the most recent and promising mechanisms of action that are distinct from existing antipsychotics. Some of the new mechanisms of action include drugs targeting the glutamatergic system, the alpha7 nicotinic acetylcholine receptor, the phosphodiesterase 10A enzyme, or the muscarinic and serotoninergic system. Finally, we have reviewed a number of alternative nonpharmacological pathways, such as avatar therapy, repetitive transcranial magnetic stimulation, or cognitive remediation. The chapter ends by discussing some of the major challenges facing the development of new treatments for psychotic disorders.

scholarly journals Exercise and Worsening of Extrapyramidal Symptoms during Treatment with Long-Acting Injectable Antipsychotics

Pharmacy ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 123
Author(s):  
David D. Kim ◽  
Donna J. Lang ◽  
Darren E. R. Warburton ◽  
Alasdair M. Barr ◽  
Randall F. White ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Exercise Program ◽  
Extrapyramidal Symptoms ◽  
Antipsychotic Treatment ◽  
Antipsychotic Medications ◽  
Treatment Regimens ◽  
Long Acting

Second-generation antipsychotic medications are used to treat schizophrenia and a range of other psychotic disorders, although adverse effects, including cardiovascular and metabolic abnormalities and extrapyramidal symptoms, are often inevitable. Studies have shown that exercise, as an adjunct therapy, can be effective in reducing the core symptoms of schizophrenia as well as ameliorating intrinsic and antipsychotic-induced cardiometabolic abnormalities. However, it is noteworthy that exercise may need to be implemented with caution in some individuals receiving certain antipsychotic treatment regimens. We report here two cases of exercise-associated worsening of extrapyramidal symptoms in two individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication over the course of a 12-week exercise program. This worsening of extrapyramidal symptoms can be attributed to an increase in blood flow to the site of injection during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 receptor blockade. When monitoring drug therapy for patients receiving long-acting injectable antipsychotic medications, pharmacists and other healthcare professionals need to consider exercise as a contributing factor for the emergence of extrapyramidal symptoms.

scholarly journals Cannabidiol as a potential treatment for psychosis

2019 ◽  
Vol 9 ◽  
pp. 204512531988191 ◽  
Author(s):  
Cathy Davies ◽  
Sagnik Bhattacharyya
Keyword(s):  
Mechanism Of Action ◽  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
Significant Proportion ◽  
D2 Receptor ◽  
Current Evidence ◽  
Novel Treatment ◽  
D2 Antagonist ◽  
Unique Mechanism ◽  
Preclinical Work

Psychotic disorders such as schizophrenia are heterogeneous and often debilitating conditions that contribute substantially to the global burden of disease. The introduction of dopamine D2 receptor antagonists in the 1950s revolutionised the treatment of psychotic disorders and they remain the mainstay of our treatment arsenal for psychosis. However, traditional antipsychotics are associated with a number of side effects and a significant proportion of patients do not achieve an adequate remission of symptoms. There is therefore a need for novel interventions, particularly those with a non-D2 antagonist mechanism of action. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action. In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders. We first review the evidence from the perspective of preclinical work and human experimental and neuroimaging studies. We then synthesise the current evidence regarding the clinical efficacy of CBD in terms of positive, negative and cognitive symptoms, safety and tolerability, and potential mechanisms by which CBD may have antipsychotic effects.

Schizophrenia drug discovery and development in an evolving era: Are new drug targets fulfilling expectations?

2015 ◽  
Vol 29 (2) ◽  
pp. 230-238 ◽  
Author(s):  
John Dunlop ◽  
Nicholas J Brandon
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Negative Symptoms ◽  
Metabotropic Glutamate Receptor ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Therapeutic Benefit ◽  
Receptor Subtype ◽  
Drug Discovery And Development ◽  
Alpha7 Nicotinic Acetylcholine Receptor

Current therapeutics for schizophrenia, the typical and atypical antipsychotic class of drugs, derive their therapeutic benefit predominantly by antagonism of the dopamine D2 receptor subtype and have robust clinical benefit on positive symptoms of the disease with limited to no impact on negative symptoms and cognitive impairment. Driven by these therapeutic limitations of current treatments and the recognition that transmitter systems beyond the dopaminergic system in particular glutamatergic transmission contribute to the etiology of schizophrenia significant recent efforts have focused on the discovery and development of novel treatments for schizophrenia with mechanisms of action that are distinct from current drugs. Specifically, compounds selectively targeting the metabotropic glutamate receptor 2/3 subtype, phosphodiesterase subtype 10, glycine transporter subtype 1 and the alpha7 nicotinic acetylcholine receptor have been the subject of intense drug discovery and development efforts. Here we review recent clinical experience with the most advanced drug candidates targeting each of these novel mechanisms and discuss whether these new agents are living up to expectations.

scholarly journals Altered emotional experiences attributed to antipsychotic medications – A potential link with estimated dopamine D2 receptor occupancy

2016 ◽  
Vol 236 ◽  
pp. 9-14 ◽  
Author(s):  
Irene M. Lako ◽  
Katja Taxis ◽  
Edwin R. van den Heuvel ◽  
Cathalijn H.C. Leenaars ◽  
Huibert Burger ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Occupancy ◽  
Emotional Experiences ◽  
Antipsychotic Medications ◽  
Dopamine D2 ◽  
Dopamine D2 Receptor Occupancy ◽  
Potential Link

Effect of amphetamine on dopamine D2 receptor binding in the primate brain with the agonist ligand [11C]MNPA

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S646-S646
Author(s):  
Nicholas Seneca ◽  
Sjoerd Finnema ◽  
Masanori Ichise ◽  
Balazs Gulyas ◽  
Håkan Wikstrom ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Primate Brain

Assessment of endocrine disorders of the hypothalamicpituitary axis by nuclear medicine techniques

2002 ◽  
Vol 41 (02) ◽  
pp. 80-90 ◽  
Author(s):  
F. Jockenhövel ◽  
P. Theissen ◽  
M. Dietlein ◽  
W. Krone ◽  
H. Schicha ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Pituitary Adenomas ◽  
Dopamine D2 Receptor ◽  
Somatostatin Receptor ◽  
D2 Receptor ◽  
Ectopic Acth Syndrome ◽  
Endocrine Disorders ◽  
Ectopic Acth ◽  
Number Of Patients ◽  
Hypothalamic Pituitary Axis

SummaryThe following article reviews nuclear medicine techniques which can be used for assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar and SPECT imaging somatostatin-receptor- and dopamine- D2-receptor-scintigraphy are the most widely distributed techniques. These nuclear medicine techniques may be indicated in selected cases to answer differential diagnostic problems. They can be helpful to search for presence and localization of receptor positive tissue. Furthermore they can detect metastasis in the rare cases of a pituitary carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal because obvious pituitary adenomas could not be visualized. Other PET radiopharmaca including C-11-methionine, C-11-tyrosine, F-18-fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in specialized centers only. Overall indications for nuclear medicine in studies for the assessment of endocrine disorders of the hypothalamic-pituitary-axis are rare. Original studies often report only about a small number of patients. According to the authors’ opinion the relevance of nuclear medicine in studies of clinically important endocrinologic fields, e. g. localization of small ACTH-producing pituitary adenomas, tumor localization in ectopic ACTH syndrome, localization of recurrent pituitary tissue, assessment of small incidentalomas, can not be definitely given yet.

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