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Biomolecules
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Drug Design and Development for Diagnosis and Treatment of Neuropsychiatric...
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Drug Design and Development for Diagnosis and Treatment of Neuropsychiatric Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 9832

Special Issue Editors

Dr. Marco Bortolato

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
Interests: animal models; impulse-control disorders; dopamine; serotonin; neurosteroids; Tourette syndrome; pathological aggression; pathological gambling
Special Issues, Collections and Topics in MDPI journals
Assoc. Prof. Simona Scheggi

E-Mail Website
Guest Editor
Dept. Molecular and Developmental Medicine, University of Siena, Siena, Italy
Interests: animal models; depression; dopamine; psychopharmacology

Special Issue Information

Dear Colleagues,

Although the incidence and economic burden of neuropsychiatric disorders are increasing worldwide, therapeutic tools for these diseases remain unsatisfactory. For example, no effective pharmacological treatments for Alzheimer’s disease, autism spectrum disorder, negative and cognitive symptoms of schizophrenia are available. Unfortunately, because of the complexity of these conditions, many clinical trials have failed, and several pharmaceutical companies have recently reduced or ceased their investment in neuroscience research. This background underscores the urgent need for tangible progress and advances in neuropsychopharmacological research.  

This Special Issue of Biomolecules is dedicated to novel directions in drug design and development for neuropsychiatric diseases. The main goal is to showcase the ongoing progress in the identification of molecular targets for the treatment of epilepsy, movement disorders, dementia, neuromuscular diseases, as well as depression, schizophrenia, anxiety, autism, and drug abuse and dependence. 

Assoc. Prof. Marco Bortolato
Assoc. Prof. Simona Scheggi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Drug development
  • Neurological disorders
  • Psychiatric disorders
  • Therapeutic target
  • Neuropsychopharmacology

Published Papers (3 papers)

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Research

18 pages, 1652 KiB  
Communication
Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D2 3,4-dihydroquinolin-2(1H)-one Derivatives Related to Aripiprazole
by Radomir Juza, Kristyna Stefkova, Wim Dehaen, Alena Randakova, Tomas Petrasek, Iveta Vojtechova, Tereza Kobrlova, Lenka Pulkrabkova, Lubica Muckova, Marko Mecava, Lukas Prchal, Eva Mezeiova, Kamil Musilek, Ondrej Soukup and Jan Korabecny
Biomolecules 2021, 11(9), 1262; https://doi.org/10.3390/biom11091262 - 24 Aug 2021
Cited by 5 | Viewed by 2867
Abstract
In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D2 (D2R) modulators were synthesized and evaluated in vitro. The preliminary structure–activity relationship disclosed that compound 5e exhibited the highest D2R affinity [...] Read more.
In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D2 (D2R) modulators were synthesized and evaluated in vitro. The preliminary structure–activity relationship disclosed that compound 5e exhibited the highest D2R affinity among the newly synthesized compounds. In addition, 5e showed a very low cytotoxic profile and a high probability to cross the blood–brain barrier, which is important considering the observed affinity. However, molecular modelling simulation revealed completely different binding mode of 5e compared to USC-D301, which might be the culprit of the reduced affinity of 5e toward D2R in comparison with USC-D301. Full article
(This article belongs to the Special Issue Drug Design and Development for Diagnosis and Treatment of Neuropsychiatric Diseases)
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13 pages, 2473 KiB  
Article
The α6 GABAA Receptor Positive Allosteric Modulator DK-I-56-1 Reduces Tic-Related Behaviors in Mouse Models of Tourette Syndrome
by Roberto Cadeddu, Daniel E. Knutson, Laura J. Mosher, Stefanos Loizou, Karen Odeh, Janet L. Fisher, James M. Cook and Marco Bortolato
Biomolecules 2021, 11(2), 175; https://doi.org/10.3390/biom11020175 - 28 Jan 2021
Cited by 11 | Viewed by 2791
Abstract
Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric [...] Read more.
Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists. Full article
(This article belongs to the Special Issue Drug Design and Development for Diagnosis and Treatment of Neuropsychiatric Diseases)
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14 pages, 1419 KiB  
Article
Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (S)-CE-123 on Mesocorticolimbic Dopamine System
by Claudia Sagheddu, Nicholas Pintori, Predrag Kalaba, Vladimir Dragačević, Gessica Piras, Jana Lubec, Nicola Simola, Maria Antonietta De Luca, Gert Lubec and Marco Pistis
Biomolecules 2020, 10(5), 779; https://doi.org/10.3390/biom10050779 - 18 May 2020
Cited by 15 | Viewed by 3279
Abstract
Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that [...] Read more.
Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that improves cognitive and motivational processes in experimental animals. We studied the neuropharmacological and behavioral effects of the S-enantiomer of CE-123 ((S)-CE-123) and R-modafinil in cognitive- and reward-related brain areas of adult male rats. In vivo single unit recordings in anesthetized animals showed that (S)-CE-123, but not R-modafinil, dose-dependently (1.25 to 10 mg/kg i.v.) reduced firing of pyramidal neurons in the infralimbic/prelimbic (IL/PrL) cortex. Neither compound the affected firing activity of ventral tegmental area dopamine cells. In freely moving animals, (S)-CE-123 (10 mg/kg i.p.) increased extracellular dopamine levels in the IL/PrL, with different patterns when compared to R-modafinil (10 mg/kg i.p.); in the nucleus accumbens shell, a low and transitory increase of dopamine was observed only after (S)-CE-123. Neither (S)-CE-123 nor R-modafinil initiated the emission of 50-kHz ultrasonic vocalizations, a behavioral marker of positive affect and drug-mediated reward. Our data support previous reports of the procognitive effects of (S)-CE-123, and show a minor impact on reward-related dopaminergic areas. Full article
(This article belongs to the Special Issue Drug Design and Development for Diagnosis and Treatment of Neuropsychiatric Diseases)
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