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.

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.

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

Epidemics and History: Multiple Approaches to the Subject

2021 ◽  
pp. 5
Author(s):  
Dmitriy Mikhel
Keyword(s):  
20Th Century ◽  
Great Influence ◽  
Medical Knowledge ◽  
Public Attention ◽  
Medical Texts ◽  
Quarter Century ◽  
History Of ◽  
The Media ◽  
New Generation ◽  
The 19Th Century

The problems of epidemics have increasingly attracted the attention of researchers in recent years. The history of epidemics has its own historiography, which dates to the physician Hippocrates and the historian Thucydides. Up to the 19th century, historians followed their ideas, but due to the progress in medical knowledge that began at that time, they almost lost interest in the problems of epidemics. In the early 20th century, due to the development of microbiology and epidemiology, a new form of the historiography of epidemics emerged: the natural history of diseases which was developed by microbiologists. At the same time, medical history was reborn, and its representatives saw their task as proving to physicians the usefulness of studying ancient medical texts. Among the representatives of the new generation of medical historians, authors who contributed to the development of the historiography of epidemics eventually emerged. By the end of the 20th century, they included many physician-enthusiasts. Since the 1970s, influenced by many factors, more and more professional historians, for whom the history of epidemics is an integral part of the history of society. The last quarter-century has also seen rapid growth in popular historiography of epidemics, made possible by the activation of various humanities researchers and journalists trying to make the history of epidemics more lively and emotional. A great influence on the spread of new approaches to the study of the history of epidemics is now being exerted by the media, focusing public attention on the new threats to human civilization in the form of modern epidemics.

scholarly journals Determining the Relative Efficacy of Positive Allosteric Modulators of the GABAA Receptor

2013 ◽  
Vol 19 (3) ◽  
pp. 462-467 ◽  
Author(s):  
Philippe Ghisdal ◽  
Nadine Noel ◽  
Nathalie Pacico ◽  
Murielle Martini ◽  
Patrik Foerch ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Patch Clamp ◽  
Multiple Drug ◽  
Allosteric Modulators ◽  
Relative Efficacy ◽  
Subtype Selectivity ◽  
Automated Patch Clamp ◽  
Positive Allosteric Modulators ◽  
New Generation ◽  
Different Levels

Gamma amino butyric acid receptors (GABA) are major therapeutic targets for the development of drugs in neurological and psychiatric disorders. The new generation of GABAA modulators is targeting subtype selectivity and low/partial efficacy on the receptor to potentially overcome the adverse effects described for drugs with full agonist profile. We evaluated a screening approach to measure the relative efficacy of GABAA positive allosteric modulators (PAM) using automated patch clamp and fluorescence membrane potential assays. We determined that the use of an internal comparator (zolpidem), tested on each cell in parallel to the test compound, provides a reliable approach to measure and compare the relative efficacy of PAM ligands. Patch clamp recordings on recombinant GABAA receptors, using a multiple drug addition protocol, allows us to rank PAM ligands with different levels of efficacies. We observed that fluorescence membrane potential assays are not predictive of the relative efficacies of GABAA PAM ligands.

scholarly journals The Study of Religious Customs and Traditions of the Nanai in Russian Science (Pre-Revolutionary Context) and the Experience of Their Systematization in the Literary Ethnography of Venedikt Mart

2020 ◽  
pp. 137-147
Author(s):  
Kseniya A. Zemlyanskaya ◽  
Keyword(s):  
Material Culture ◽  
19Th Century ◽  
Russian Far East ◽  
Far East ◽  
Literary Form ◽  
Russian Science ◽  
Close Study ◽  
Wedding Ceremony ◽  
New Generation ◽  
The 19Th Century

In the 19th – early 20th centuries, the Nanai were one of the largest Tungus-Manchu peoples of the Russian Far East. A close study of their traditions and customs began in the middle of the 19th century, when numerous ethnographic expeditions of researchers (L.I. Shrenk, R.K. Maak, K.I. Maksimovich) were sent to the Amur. First of all, the researchers were interested in the material culture of the Nanai, the issues of religion were touched upon in the mainstream of ethnographic research. In the last quarter of the 19th century, the attention of researchers was directed to the description of Nanai rites of passage (D. Kropotkin, P.P. Shimkevich). Scientific expeditions of the early 20th century were aimed at describing the spiritual culture of the Nanai and its reflection in material culture (I.A. Lopatin, L.Ya. Sternberg). The description of the religious beliefs of the Nanai was recorded as a result of the missionary activities of Blagoveshchensk and Vladivostok dioceses. In 1932, the former Far East writer Venedikt Mart published the story “Dere – the Water Wedding”, where he accumulates and systematizes the accumulated knowledge about the Nanai people in literary form, introducing certain elements of fiction. Despite the fact that Venedikt Mart writes about the denial of religious customs and traditions by the new generation of Nanai, nevertheless, the story itself is, in fact, clearly fixed at its core by the content of the wedding ceremony

scholarly journals A knowledge network for a dynamic taxonomy of psychiatric disease

2015 ◽  
Vol 17 (1) ◽  
pp. 79-87 ◽  
Keyword(s):  
Mental Disorders ◽  
Strategic Plan ◽  
Research Community ◽  
Mental Illnesses ◽  
Knowledge Network ◽  
Psychiatric Disease ◽  
The Novel ◽  
Research Domain Criteria ◽  
Novel Approach ◽  
Research Domain

The Research Domain Criteria (RDoC) project was initiated by the National Institute of Mental Health (NIMH) in early 2009 as the implementation of Goal 1.4 of its just-issued strategic plan. In keeping with the NIMH mission, to "transform the understanding and treatment of mental illnesses through basic and clinical research," RDoC was explicitly conceived as a research-related initiative. The statement of the relevant goal in the strategic plan reads: "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures." Due to the novel approach that RDoC takes to conceptualizing and studying mental disorders, it has received widespread attention, well beyond the borders of the immediate research community. This review discusses the rationale for the experimental framework that RDoC has adopted, and its implications for the nosology of mental disorders in the future.

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

Working the machinery

2021 ◽  
pp. 132-155
Author(s):  
Jens Steffek
Keyword(s):  
International Development ◽  
Regional Integration ◽  
Political Scientist ◽  
Human Welfare ◽  
The 1950S ◽  
United Nations System ◽  
American Political Scientist ◽  
Technical Solutions ◽  
New Generation ◽  
The 19Th Century

This chapter explores how technocratic internationalism found new fields of application in international development and regional integration. During the 1950s and 1960s, a new generation of international organizations began to work on the socio-economic tasks that functionalists had recommended for international action. With the expansion of the United Nations system of organization, global governance took a markedly technocratic but also a welfarist turn. In this explicit orientation towards human welfare and concrete projects, they differed from the technical standard setting organizations active since the 19th century. The concept of socio-economic development was congenial to functionalists since its promise of progress is linked to the technocratic belief in technical solutions. Functionalism also became a textbook doctrine for European integration, with the European Coal and Steel Community of 1951 as a direct product of functionalist thinking. This chapter also discusses the professionalization of political science in the 1950s and 1960s, where scholars began to perceive Mitrany’s ideas as ‘reformist ideology’ rather than as a serious theory of international organization. To remedy these defects, American political scientist Ernst Haas re-formulated it as ‘neo-functionalism’. Although ostensibly an empirical-analytical approach eschewing normative commitments, neo-functionalism remained committed to the ideal of rationalized governance.

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