scholarly journals Antipsychotic drugs disrupt normal development in Caenorhabditis elegans via additional mechanisms besides dopamine and serotonin receptors

2006 ◽  
Vol 54 (5) ◽  
pp. 361-372 ◽  
Author(s):  
Dallas R. Donohoe ◽  
Eric J. Aamodt ◽  
Elizabeth Osborn ◽  
Donard S. Dwyer
Keyword(s):  
Caenorhabditis Elegans ◽  
Serotonin Receptors ◽  
Antipsychotic Drugs ◽  
Normal Development ◽  
Dopamine And Serotonin Receptors

Recent development of piperazine and piperidine derivatives as antipsychotic agents

2020 ◽  
Vol 20 ◽  
Author(s):  
Akash Rathore ◽  
Vivek Asati ◽  
Sushil Kumar Kashaw ◽  
Shivangi Agarwal ◽  
Deepa Parwani ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Atypical Antipsychotics ◽  
Antipsychotic Drugs ◽  
Antipsychotic Agents ◽  
Anti Psychotic ◽  
Lead Compounds ◽  
Piperazine Derivatives ◽  
Structure Activity ◽  
Dopamine And Serotonin Receptors ◽  
Global Population

: Schizophrenia is a chronic neuropsychiatric disorder that affects nearly 1% of the global population. There are various anti-psychotic drugs available for the treatment of schizophrenia, but they have certain side effects, therefore there is a need to explore and develop novel potential lead compounds against schizophrenia. The currently available drugs e.g. typical and atypical antipsychotics act on different dopamine and serotonin receptors and as per literature reports, various piperidine and piperazine derivatives have shown promising activity against these receptors. When different heterocyclic groups are attached to basic piperidine and piperazine rings, the anti-psychotic activity is greatly potentiated. In this direction various antipsychotic drugs have been synthesized at laboratory level and few are under clinical trial studies such as Lu AE58054, PF-04802540, ORG25935, DMXB-A, Bitopertin and ABT-126. In the present review, we include the studies related to the effect of different substituents on piperidine/piperazine derivatives and their anti-psychotic activity. Various series of synthesized compounds by different researchers with piperidine/piperazine nucleus have been reviewed and diagrammatically represented in the form of SAR (structure activity relationships) which will help to the scientists for the development of potential lead compounds.

scholarly journals Behavioral and Psychological Symptoms in Dementia (BPSD) and the Use of Antipsychotics

2021 ◽  
Vol 14 (3) ◽  
pp. 246
Author(s):  
Valeria Calsolaro ◽  
Grazia Daniela Femminella ◽  
Sara Rogani ◽  
Salvatore Esposito ◽  
Riccardo Franchi ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Psychological Symptoms ◽  
Rebound Effect ◽  
Safety Issues ◽  
Second Generation Antipsychotics ◽  
Therapy Interruption ◽  
Dopamine And Serotonin Receptors ◽  
Behavioral And Psychological Symptoms

Dementia affects about 47 million people worldwide, number expected to exponentially increase within 30 years. Alzheimer’s disease (AD) is the most common dementia type, accounting on its own for almost 70% of all dementia cases. Behavioral and psychological symptoms (BPSD) frequently occur during the disease progression; to treat agitation, aggressiveness, delusions and hallucinations, the use of antipsychotic drugs should be limited, due to their safety issues. In this literature review regarding the use of antipsychotics for treating BPSD in dementia, the advantages and limitation of antipsychotic drugs have been evaluated. The available medications for the management of behavioral and psychological symptoms are the antipsychotics, classed into typical and atypical, depending on their action on dopamine and serotonin receptors. First generation, or typical, antipsychotics exhibit lack of tolerability and display a broad range of side effects such as sedation, anticholinergic effects and extrapyramidal symptoms. Atypical, or second generation, antipsychotics bind more selectively to dopamine receptors and simultaneously block serotonin receptors, resulting in higher tolerability. High attention should be paid to the management of therapy interruption or switch between antipsychotics, to limit the possible rebound effect. Several switching strategies may be adopted, and clinicians should “tailor” therapies, accounting for patients’ symptoms, comorbidities, polytherapies and frailty.

Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain

Synapse ◽  
1990 ◽  
Vol 6 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Steven J. O'Dell ◽  
Gerald J. Lahoste ◽  
Clifford B. Widmark ◽  
Raymond M. Shapiro ◽  
Steven G. Potkin ◽  
...  
Keyword(s):  
Rat Brain ◽  
Serotonin Receptors ◽  
Chronic Treatment ◽  
Dopamine And Serotonin Receptors

Effect of carbidine on dopamine and serotonin receptors of the CNS

1985 ◽  
Vol 99 (6) ◽  
pp. 754-756 ◽  
Author(s):  
A. M. Zharkovskii ◽  
N. E. Klassen ◽  
T. A. Zharkovskaya
Keyword(s):  
Serotonin Receptors ◽  
Dopamine And Serotonin Receptors

Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors

2021 ◽  
Author(s):  
Janine Naß ◽  
Thomas Efferth
Keyword(s):  
Caenorhabditis Elegans ◽  
In Silico ◽  
Serotonin Receptors ◽  
New Drugs ◽  
Potential Candidate ◽  
Human Beings ◽  
Wild Type ◽  
C Elegans ◽  
Stress Symptoms ◽  
Serotonin System

Abstract Introduction Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. Methods WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. Results WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. Limitations Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. Conclusion WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.

scholarly journals Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics

2020 ◽  
Vol 13 (11) ◽  
pp. 388
Author(s):  
Irene Fasciani ◽  
Francesco Petragnano ◽  
Gabriella Aloisi ◽  
Francesco Marampon ◽  
Marco Carli ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Atypical Antipsychotics ◽  
Binding Pocket ◽  
Mental Illnesses ◽  
Psychiatric Disease ◽  
Allosteric Modulators ◽  
New Class ◽  
Dopamine And Serotonin Receptors ◽  
New Generation ◽  
The 19Th Century

Schizophrenia was first described by Emil Krapelin in the 19th century as one of the major mental illnesses causing disability worldwide. Since the introduction of chlorpromazine in 1952, strategies aimed at modifying the activity of dopamine receptors have played a major role for the treatment of schizophrenia. The introduction of atypical antipsychotics with clozapine broadened the range of potential targets for the treatment of this psychiatric disease, as they also modify the activity of the serotoninergic receptors. Interestingly, all marketed drugs for schizophrenia bind to the orthosteric binding pocket of the receptor as competitive antagonists or partial agonists. In recent years, a strong effort to develop allosteric modulators as potential therapeutic agents for schizophrenia was made, mainly for the several advantages in their use. In particular, the allosteric binding sites are topographically distinct from the orthosteric pockets, and thus drugs targeting these sites have a higher degree of receptor subunit specificity. Moreover, “pure” allosteric modulators maintain the temporal and spatial fidelity of native orthosteric ligand. Furthermore, allosteric modulators have a “ceiling effect”, and their modulatory effect is saturated above certain concentrations. In this review, we summarize the progresses made in the identification of allosteric drugs for dopamine and serotonin receptors, which could lead to a new generation of atypical antipsychotics with a better profile, especially in terms of reduced side effects.

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