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Novel Compounds in the Treatment of the CNS Disorders

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 43339

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Prof. Dr. Ewa Poleszak

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Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
Interests: depression; anxiety; preclinical study; neuropharmacology; neuropsychopharmacology; toxicological and biochemical analysis
Special Issues, Collections and Topics in MDPI journals

Dr. Anna Serefko

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Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
Interests: depression; anxiety; epilepsy; neuroscience; preclinical studies
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Aleksandra Szopa

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Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
Interests: depression; anxiety; epilepsy; neuroscience; preclinical studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Central nervous system (CNS) disorders are a broad group of neurological conditions affecting the functioning of the brain or spinal cord and in consequence, deteriorating quality of life of a given patient. Amongst them, bipolar disorder, depression, epilepsy/seizures, migraine, Parkinson's disease, Alzheimer's disease, Huntington's disease, attention deficit/hyperactivity disorder, and multiple sclerosis are most frequently diagnosed. These neurological conditions can be caused by several different factors, such as stroke, trauma, infections, autoimmune disorders, tumors, brain or spinal cord degeneration, structural defects or genetic determinants. Despite enormous progress in medicine and pharmacotherapy, management of the CNS diseases is still challenging: most of these disorders cannot be thoroughly cured, not all patients achieve even a partial remission, prescribed drugs induce troublesome side effects. Therefore, continuous attempts have been made to develop new treatment strategies and safer more effective drugs. Research and medical teams focus on diverse treatment options: innovative compounds, combinations of well-known substances and surgical and neurorehabilitation procedures. In our Special Issue on Novel Compounds in the Treatment of the CNS Disorders, we aim to bring together experts working in the field of neurological conditions and invite them to present their recent results from both pre-clinical and clinical studies related to pharmacotherapy of CNS disorders. Review articles and short communications on the latest achievements in the management of CNS disorders are also welcome.

Prof. Dr. Ewa Poleszak
Dr. Anna Serefko
Dr. Aleksandra Szopa
Guest Editors

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Keywords

ADHD
autism
depression
epilepsy
neurodegenerative diseases
neuroscience
preclinical studies
clinical studies

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Novel Compounds in the Treatment of the CNS Disorders, 2nd Edition in Molecules

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Research

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18 pages, 2002 KiB

Open AccessArticle

Neuroprotective Effect of Yucca schidigera Roezl ex Ortgies Bark Phenolic Fractions, Yuccaol B and Gloriosaol A on Scopolamine-Induced Memory Deficits in Zebrafish

by Łukasz Pecio, Solomiia Kozachok, Ion Brinza, Razvan Stefan Boiangiu, Lucian Hritcu, Cornelia Mircea, Ana Flavia Burlec, Oana Cioanca, Monica Hancianu, Olga Wronikowska-Denysiuk, Krystyna Skalicka-Woźniak and Wiesław Oleszek

Molecules 2022, 27(12), 3692; https://doi.org/10.3390/molecules27123692 - 8 Jun 2022

Cited by 7 | Viewed by 2593

Abstract

Y. schidigera contains a number of unusual polyphenols, derivatives of resveratrol and naringenin, called spiro-flavostilbenoids, which have potent in vitro anti-inflammatory, antioxidant, and moderate cholinesterase inhibitory activities. To date, these compounds have not been tested in vivo for the treatment of neurodegenerative diseases. The aim of the present study was to evaluate the effects of both single spiro-flavostilbenoids (yuccaol B and gloriosaol A) and phenolic fractions derived from Y. schidigera bark on scopolamine-induced anxiety and memory process deterioration using a Danio rerio model. Detailed phytochemical analysis of the studied fractions was carried out using different chromatographic techniques and Nuclear Magnetic Resonance (NMR). The novel tank diving test was used as a method to measure zebrafish anxiety, whereas spatial working memory function was assessed in Y-maze. In addition, acetylcholinesterase/butyrylcholinesterase (AChE/BChE) and 15-lipooxygenase (15-LOX) inhibition tests were performed in vitro. All pure compounds and fractions under study exerted anxiolytic and procognitive action. Moreover, strong anti-oxidant capacity was observed, whereas weak inhibition towards cholinesterases was found. Thus, we may conclude that the observed behavioral effects are complex and result rather from inhibition of oxidative stress processes and influence on cholinergic muscarinic receptors (both 15-LOX and scopolamine assays) than effects on cholinesterases. Y. schidigera is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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12 pages, 2863 KiB

Open AccessArticle

Effect of Co-Treatment of Olanzapine with SEP-363856 in Mice Models of Schizophrenia

by Lingzhi Liang, Xia Ren, Junyi Xu, Yurong Ma, Yunlin Xue, Tao Zhuang and Guisen Zhang

Molecules 2022, 27(8), 2550; https://doi.org/10.3390/molecules27082550 - 14 Apr 2022

Cited by 11 | Viewed by 3092

Abstract

Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED₃₀ (3 mg/kg) was significantly smaller (p < 0.05) than the theoretical ED₃₀ (5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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18 pages, 2714 KiB

Open AccessArticle

Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal

by Joanna Listos, Piotr Listos, Irena Baranowska-Bosiacka, Agata Karpiuk, Joanna Filarowska, Małgorzata Łupina, Tymoteusz Słowik, Sylwia Zawiślak and Jolanta Kotlińska

Molecules 2022, 27(8), 2478; https://doi.org/10.3390/molecules27082478 - 12 Apr 2022

Cited by 11 | Viewed by 3163

Abstract

(1) Background: Recent data indicate that receptors for GLP-1 peptide are involved in the activity of the mesolimbic system. Thus, the purpose of the present study was to examine the effect of the selective dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on morphine dependence in mice. (2) Methods: Morphine dependence in mice was obtained by administration of increasing doses of morphine for eight consecutive days, twice a day. On the 9th day of the experiment, the naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (jumping) were assessed. Moreover, behavioral effects of short-term (60 h after morphine discontinuation) and long-term (14 days after morphine discontinuation) morphine withdrawal were observed. In terms of behavioral effects, the depressive effect in the forced swim test and anxiety in the elevated plus maze test were investigated. Locomotor activity of mice was also studied. (3) Results: The administration of linagliptin (10 and 20 mg/kg, ip) for 8 consecutive days before morphine injections significantly diminished the number of naloxone-induced morphine withdrawal signs (jumping) in mice. In addition, the cessation of morphine administration induced depressive behavior in mice which were observed during short- and long-term morphine withdrawal. Linagliptin administered during morphine withdrawal significantly reduced the depressive behavior in studied mice. Furthermore, the short-term morphine withdrawal evoked anxiety which also was reduced by linagliptin in mice. (4) Conclusions: The present study reveals that GLP-1 receptors are involved in morphine dependence. What is more, linagliptin might be a valuable drug in attenuating the physical symptoms of morphine dependence. It might be also a useful drug in reducing emotional disturbances which may develop during the morphine withdrawal period. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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19 pages, 3934 KiB

Open AccessArticle

Antidepressant-like Effects of Combined Fluoxetine and Zinc Treatment in Mice Exposed to Chronic Restraint Stress Are Related to Modulation of Histone Deacetylase

by Paulina Misztak, Magdalena Sowa-Kućma, Patrycja Pańczyszyn-Trzewik, Bernadeta Szewczyk and Gabriel Nowak

Molecules 2022, 27(1), 22; https://doi.org/10.3390/molecules27010022 - 21 Dec 2021

Cited by 10 | Viewed by 5438

Abstract

Chronic stress is the key factor contributing to the development of depressive symptoms. Chronic restraint stress (CRS) is well validated and is one of the most commonly used models to induce depressive-like behavior in rodents. The present study aimed to evaluate whether fluoxetine (FLU 5 mg/kg) and zinc (Zn 10mg/kg) given simultaneously induce a more pronounced antidepressant-like effect in the CRS model than both those compounds given alone. Behavioral assessment was performed using the tail suspension and splash tests (TST and ST, respectively). Furthermore, the effects of CRS, FLU and Zn given alone and combined treatment with FLU + Zn on the expression of proteins involved in the apoptotic, inflammatory, and epigenetic processes were evaluated in selected brain structures (prefrontal cortex, PFC; and hippocampus, Hp) using Western blot analysis or enzyme-linked immunosorbent assays (ELISA). The results obtained indicated that three hours (per day) of immobilization for 4 weeks induced prominent depressive symptoms that manifested as increased immobility time in the TST, as well as decreased number and grooming time in the ST. Behavioral changes induced by CRS were reversed by both FLU (5 and 10 mg/kg) or Zn (10 mg/kg). Zinc supplementation (10 mg/kg) slightly increases the effectiveness of FLU (5 mg/kg) in the TST. However, it significantly increased the activity of FLU in the ST compared to the effect induced by FLU and Zn alone. Biochemical studies revealed that neither CRS nor FLU and Zn given alone or in combined treatment alter the expression of proteins involved in apoptotic or inflammatory processes. CRS induced major alterations in histone deacetylase (HDAC) levels by increasing the level of HADC1 and decreasing the level of HADC4 in the PFC and Hp, decreasing the level of HADC6 in the PFC but increasing it in Hp. Interestingly, FLU + Zn treatment reversed CRS-induced changes in HDAC levels in the Hp, indicating that HDAC modulation is linked to FLU + Zn treatment and this effect is structure-specific. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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17 pages, 42568 KiB

Open AccessArticle

Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

by Derya Osmaniye, Berkant Kurban, Begüm Nurpelin Sağlık, Serkan Levent, Yusuf Özkay and Zafer Asım Kaplancıklı

Molecules 2021, 26(21), 6640; https://doi.org/10.3390/molecules26216640 - 2 Nov 2021

Cited by 14 | Viewed by 2531

Abstract

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC₅₀ value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The K_i values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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19 pages, 1753 KiB

Open AccessArticle

Cannabidiol Attenuates MK-801-Induced Cognitive Symptoms of Schizophrenia in the Passive Avoidance Test in Mice

by Marta Kruk-Slomka and Grazyna Biala

Molecules 2021, 26(19), 5977; https://doi.org/10.3390/molecules26195977 - 2 Oct 2021

Cited by 19 | Viewed by 3271

Abstract

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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9 pages, 2063 KiB

Open AccessArticle

Synthesis of Proposed Structure of Aaptoline A, a Marine Sponge-Derived 7,8-Dihydroxyquinoline, and Its Neuroprotective Properties in C. elegans

by Soobin Kim, Wooin Yang, Dong Seok Cha and Young Taek Han

Molecules 2021, 26(19), 5964; https://doi.org/10.3390/molecules26195964 - 1 Oct 2021

Cited by 6 | Viewed by 2270

Abstract

A concise and efficient synthesis of the proposed structure of aaptoline A, a 7,8-dihydroxyquinoline derived from a marine sponge, was accomplished in seven steps with a 52% overall yield. A key feature of the synthesis is the high-yielding Ag(I)-catalyzed cycloisomerization of the N-propargylaniline precursor to afford the quinoline carboxylate skeleton from acid-labile methyl aminobenzoate. However, the spectral data of the synthesized aaptoline A were not consistent with those of previous studies. The structure of the synthesized aaptoline A was confirmed by combined 2D NMR analysis. Additional studies on the bioactivity of the synthesized aaptoline A revealed that it has the ability to protect dopaminergic neurons against MPP⁺-induced neurotoxicity in C. elegans. In addition, impaired food-sensing ability and travel distance capability in C. elegans were significantly ameliorated by aaptoline A treatment, suggesting that aaptoline A can protect dopaminergic neurons both morphologically and functionally. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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14 pages, 1173 KiB

Open AccessArticle

Effect of Ellagic Acid on Seizure Threshold in Two Acute Seizure Tests in Mice

by Mateusz Pieróg, Katarzyna Socała, Elżbieta Wyska, Ewa Poleszak and Piotr Wlaź

Molecules 2021, 26(16), 4841; https://doi.org/10.3390/molecules26164841 - 10 Aug 2021

Cited by 8 | Viewed by 3048

Abstract

Ellagic acid (EA) is a natural dietary polyphenol that has many beneficial properties, including anti-inflammatory, antioxidant, antiviral, antibacterial, and neuroprotective effects. Studies have revealed that EA may modulate seizure activity in chemically induced animal models of seizures. Therefore, the aim of the present study was to investigate the effect of EA on the seizure threshold in two acute seizure tests in male mice, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test and in the maximal electroshock seizure threshold (MEST) test. The obtained results showed that EA (100 mg/kg) significantly elevated the threshold for both the first myoclonic twitch and generalized clonic seizure in the i.v. PTZ seizure test. At the highest dose tested (200 mg/kg), EA increased the threshold for tonic hindlimb extension in the MEST test. EA did not produce any significant changes in motor coordination (assessed in the chimney test) or muscular strength (investigated in the grip-strength test). The plasma and total brain concentration-time profiles of EA after intraperitoneal and oral administration were also determined. Although further studies are necessary to confirm the anticonvulsant activity of EA, our findings suggest that it may modulate seizure susceptibility in animal models. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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17 pages, 2772 KiB

Open AccessArticle

Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation

by Rita Rosado-Ramos, Joana Godinho-Pereira, Daniela Marques, Inês Figueira, Tiago Fleming Outeiro, Regina Menezes and Cláudia Nunes dos Santos

Molecules 2021, 26(11), 3353; https://doi.org/10.3390/molecules26113353 - 2 Jun 2021

Cited by 15 | Viewed by 4636

Abstract

Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP⁺)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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Review

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12 pages, 816 KiB

Open AccessReview

The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

by Fábio Rodrigues de Oliveira, Nágila Monteiro da Silva, Moisés Hamoy, Maria Elena Crespo-López, Irlon Maciel Ferreira, Edilene Oliveira da Silva, Barbarella de Matos Macchi and José Luiz Martins do Nascimento

Molecules 2022, 27(11), 3595; https://doi.org/10.3390/molecules27113595 - 4 Jun 2022

Cited by 6 | Viewed by 2642

Abstract

Seizures and epilepsy are some of the most common serious neurological disorders, with approximately 80% of patients living in developing/underdeveloped countries. However, about one in three patients do not respond to currently available pharmacological treatments, indicating the need for research into new anticonvulsant drugs (ACDs). The GABAergic system is the main inhibitory system of the brain and has a central role in seizures and the screening of new ACD candidates. It has been demonstrated that the action of agents on endocannabinoid receptors modulates the balance between excitatory and inhibitory neurotransmitters; however, studies on the anticonvulsant properties of endocannabinoids from plant oils are relatively scarce. The Amazon region is an important source of plant oils that can be used for the synthesis of new fatty acid amides, which are compounds analogous to endocannabinoids. The synthesis of such compounds represents an important approach for the development of new anticonvulsant therapies. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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18 pages, 343 KiB

Open AccessReview

Common Factors of Alzheimer’s Disease and Rheumatoid Arthritis—Pathomechanism and Treatment

by Paulina Trzeciak, Mariola Herbet and Jarosław Dudka

Molecules 2021, 26(19), 6038; https://doi.org/10.3390/molecules26196038 - 5 Oct 2021

Cited by 11 | Viewed by 3278

Abstract

The accumulation of amyloid plaques, or misfolded fragments of proteins, leads to the development of a condition known as amyloidosis, which is clinically recognized as a systemic disease. Amyloidosis plays a special role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease, and rheumatoid arthritis (RA). The occurrence of amyloidosis correlates with the aging process of the organism, and since nowadays, old age is determined by the comfort of functioning and the elimination of unpleasant disease symptoms in the elderly, exposure to this subject is justified. In Alzheimer’s disease, amyloid plaques negatively affect glutaminergic and cholinergic transmission and loss of sympathetic protein, while in RA, amyloids stimulated by the activity of the immune system affect the degradation of the osteoarticular bond. The following monograph draws attention to the over-reactivity of the immune system in AD and RA, describes the functionality of the blood–brain barrier as an intermediary medium between RA and AD, and indicates the direction of research to date, focusing on determining the relationship and the cause–effect link between these disorders. The paper presents possible directions for the treatment of amyloidosis, with particular emphasis on innovative therapies. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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37 pages, 3375 KiB

Open AccessReview

Targeting Monoacylglycerol Lipase in Pursuit of Therapies for Neurological and Neurodegenerative Diseases

by Anca Zanfirescu, Anca Ungurianu, Dragos Paul Mihai, Denise Radulescu and George Mihai Nitulescu

Molecules 2021, 26(18), 5668; https://doi.org/10.3390/molecules26185668 - 18 Sep 2021

Cited by 16 | Viewed by 5475

Abstract

Neurological and neurodegenerative diseases are debilitating conditions, and frequently lack an effective treatment. Monoacylglycerol lipase (MAGL) is a key enzyme involved in the metabolism of 2-AG (2-arachidonoylglycerol), a neuroprotective endocannabinoid intimately linked to the generation of pro- and anti-inflammatory molecules. Consequently, synthesizing selective MAGL inhibitors has become a focus point in drug design and development. The purpose of this review was to summarize the diverse synthetic scaffolds of MAGL inhibitors concerning their potency, mechanisms of action and potential therapeutic applications, focusing on the results of studies published in the past five years. The main irreversible inhibitors identified were derivatives of hexafluoroisopropyl alcohol carbamates, glycol carbamates, azetidone triazole ureas and benzisothiazolinone, whereas the most promising reversible inhibitors were derivatives of salicylketoxime, piperidine, pyrrolidone and azetidinyl amides. We reviewed the results of in-depth chemical, mechanistic and computational studies on MAGL inhibitors, in addition to the results of in vitro findings concerning selectivity and potency of inhibitors, using the half maximal inhibitory concentration (IC₅₀) as an indicator of their effect on MAGL. Further, for highlighting the potential usefulness of highly selective and effective inhibitors, we examined the preclinical in vivo reports regarding the promising therapeutic applications of MAGL pharmacological inhibition. Full article

(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)

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