Current Neuropharmacology最新文献

{"title":"Sex-Dependent Synergism of an Edible THC: CBD Formulation in Reducing Anxiety and Depressive-like Symptoms Following Chronic Stress.","authors":"Enzo Pérez-Valenzuela, Roger Hudson, Taygun Uzuneser, Marta De Felice, Hanna Szkudlarek, Walter Rushlow, Steven R Laviolette","doi":"10.2174/1570159X21666230912101441","DOIUrl":"10.2174/1570159X21666230912101441","url":null,"abstract":"<p><p>Cannabis has shown therapeutic potential in mood and anxiety-related pathologies. However, the two primary constituents of cannabis, cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC) produce distinct effects on molecular pathways in neural circuits associated with affective disorders. Moreover, it has been proposed that the combination of THC: and CBD may have unique synergistic properties. In the present study, the effects of a 1:100 THC: CBD ratio edible formulation were tested in behavioural, neuronal and molecular assays for anxiety and depressive-like endophenotypes. Adult male and female Sprague-Dawley rats were stressed for 14 days. Then, for three weeks, open field, elevated plus maze, light/dark box, social interaction, sucrose preference, and the forced swim test were performed 90 minutes after acute consumption of CBD (30 mg/kg), THC (0.3 mg/kg), or 1:100 combination of THC:CBD. After behavioural tests, in vivo, neuronal electrophysiological analyses were performed in the ventral tegmental area and prefrontal cortex (PFC). Furthermore, western-blot experiments examined the expression of biomarkers associated with mood and anxiety disorders, including protein kinase B (Akt), glycogen synthase kinase-3 (GSK-3), BDNF, mTOR, D1, and D2 receptor in nucleus accumbens (NAc) and PFC.Edible THC:CBD produces significant anxiolytic and antidepressant effects only in stressed male rats. In most cases, the combination of THC and CBD had stronger effects than either phytochemical alone. These synergistic effects are associated with alterations in Akt/GSK3 and D2-R expression in NAc and BDNF expression in PFC. Furthermore, THC:CBD reverses chronic stress-induced alterations in PFC neuronal activity. These findings demonstrate a novel synergistic potential for THC:CBD edible formulations in stress-related pathologies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"2059-2078"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.","authors":"Bedaballi Dey, Arvind Kumar, Anant Bahadur Patel","doi":"10.2174/1570159X21666230824091601","DOIUrl":"10.2174/1570159X21666230824091601","url":null,"abstract":"<p><p>Amyotrophic Lateral Sclerosis (ALS) is the most common, adult-onset, progressive motor neurodegenerative disorder that results in death within 3 years of the clinical diagnosis. Due to the clinicopathological heterogeneity, any reliable biomarkers for diagnosis or prognosis of ALS have not been identified till date. Moreover, the only three clinically approved treatments are not uniformly effective in slowing the disease progression. Over the last 15 years, there has been a rapid advancement in research on the complex pathomechanistic landscape of ALS that has opened up new avenues for successful clinical translation of targeted therapeutics. Multiple studies suggest that the age-dependent interaction of risk-associated genes with environmental factors and endogenous modifiers is critical to the multi-step process of ALS pathogenesis. In this review, we provide an updated discussion on the dysregulated cross-talk between intracellular homeostasis processes, the unique molecular networks across selectively vulnerable cell types, and the multisystemic nature of ALS pathomechanisms. Importantly, this work highlights the alteration in epigenetic and epitranscriptomic landscape due to gene-environment interactions, which have been largely overlooked in the context of ALS pathology. Finally, we suggest that precision medicine research in ALS will be largely benefitted from the stratification of patient groups based on the clinical phenotype, onset and progression, genome, exposome, and metabolic identities.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1778-1806"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10068498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on the Importance of MiRNA-206 in the Animal Model and Human Diseases.","authors":"Wang Qi, Wei Guan","doi":"10.2174/1570159X21666230407124146","DOIUrl":"10.2174/1570159X21666230407124146","url":null,"abstract":"<p><p>MicroRNA-206 (miR-206) is a microRNA that is involved in many human diseases, such as myasthenia gravis, osteoarthritis, depression, cancers, etc. Both inhibition effects and progression roles of miR-206 have been reported for the past few years. High expression of miR-206 was observed in patients with osteoarthritis, gastric cancer and epithelial ovarian cancer compared to normal people. The study also showed that miR-206 promotes cancer progression in breast cancer patients and avascular necrosis of the femoral head. Meanwhile, several studies have shown that expression levels of miR-206 were down-regulated in laryngeal carcinoma cell multiplication, as well as in hepatocellular carcinoma, non-small lung cancer and infantile hemangioma. Moreover, miR-206 was up-regulated in the mild stage of amyotrophic lateral sclerosis patients and then down-regulated in the moderate and severe stages, indicating that miR-206 has the double effects of starting and aggravating the disease. In neuropsychiatric disorders, such as depression, miR-206 also plays an important role in the progression of the disease; the level of miR-206 is most highly expressed in the brains of patients with depression. In the current review, we summarize the role of miR-206 in various diseases, and miR-206 may be developed as a new biomarker for diagnosing diseases in the near future.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1064-1079"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut-Brain Axis and the Microbiome in Anxiety Disorders, Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder.","authors":"Marnie MacKay, Bohan H Yang, Serdar M Dursun, Glen B Baker","doi":"10.2174/1570159X21666230222092029","DOIUrl":"10.2174/1570159X21666230222092029","url":null,"abstract":"<p><p>A large body of research supports the role of stress in several psychiatric disorders in which anxiety is a prominent symptom. Other research has indicated that the gut microbiome-immune system- brain axis is involved in a large number of disorders and that this axis is affected by various stressors. The focus of the current review is on the following stress-related disorders: generalized anxiety disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder and obsessivecompulsive disorder. Descriptions of systems interacting in the gut-brain axis, microbiome-derived molecules and of pro- and prebiotics are given. Preclinical and clinical studies on the relationship of the gut microbiome to the psychiatric disorders mentioned above are reviewed. Many studies support the role of the gut microbiome in the production of symptoms in these disorders and suggest the potential for pro- and prebiotics for their treatment, but there are also contradictory findings and concerns about the limitations of some of the research that has been done. Matters to be considered in future research include longer-term studies with factors such as sex of the subjects, drug use, comorbidity, ethnicity/ race, environmental effects, diet, and exercise taken into account; appropriate compositions of pro- and prebiotics; the translatability of studies on animal models to clinical situations; and the effects on the gut microbiome of drugs currently used to treat these disorders. Despite these challenges, this is a very active area of research that holds promise for more effective, precision treatment of these stressrelated disorders in the future.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"866-883"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Stress Response: Classical Mechanisms and Beyond.","authors":"Georgia E Hodes, Debra Bangasser, Ioannis Sotiropoulos, Nikolaos Kokras, Christina Dalla","doi":"10.2174/1570159X22666231005090134","DOIUrl":"10.2174/1570159X22666231005090134","url":null,"abstract":"<p><p>Neuropsychiatric disorders, which are associated with stress hormone dysregulation, occur at different rates in men and women. Moreover, nowadays, preclinical and clinical evidence demonstrates that sex and gender can lead to differences in stress responses that predispose males and females to different expressions of similar pathologies. In this curated review, we focus on what is known about sex differences in classic mechanisms of stress response, such as glucocorticoid hormones and corticotrophin-releasing factor (CRF), which are components of the hypothalamicpituitary- adrenal (HPA) axis. Then, we present sex differences in neurotransmitter levels, such as serotonin, dopamine, glutamate and GABA, as well as indices of neurodegeneration, such as amyloid β and Tau. Gonadal hormone effects, such as estrogens and testosterone, are also discussed throughout the review. We also review in detail preclinical data investigating sex differences caused by recentlyrecognized regulators of stress and disease, such as the immune system, genetic and epigenetic mechanisms, as well neurosteroids. Finally, we discuss how understanding sex differences in stress responses, as well as in pharmacology, can be leveraged into novel, more efficacious therapeutics for all. Based on the supporting evidence, it is obvious that incorporating sex as a biological variable into preclinical research is imperative for the understanding and treatment of stress-related neuropsychiatric disorders, such as depression, anxiety and Alzheimer's disease.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"475-494"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.","authors":"David Zarate-Lopez, Ana Laura Torres-Chávez, Alma Yadira Gálvez-Contreras, Oscar Gonzalez-Perez","doi":"10.2174/1570159X22666231003121513","DOIUrl":"10.2174/1570159X22666231003121513","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increased prevalence and incidence in recent decades. Its etiology remains largely unclear, but it seems to involve a strong genetic component and environmental factors that, in turn, induce epigenetic changes during embryonic and postnatal brain development. In recent decades, clinical studies have shown that inutero exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug, is an environmental factor associated with an increased risk of ASD. Subsequently, prenatal VPA exposure in rodents has been established as a reliable translational model to study the pathophysiology of ASD, which has helped demonstrate neurobiological changes in rodents, non-human primates, and brain organoids from human pluripotent stem cells. This evidence supports the notion that prenatal VPA exposure is a valid and current model to replicate an idiopathic ASD-like disorder in experimental animals. This review summarizes and describes the current features reported with this animal model of autism and the main neurobiological findings and correlates that help elucidate the pathophysiology of ASD. Finally, we discuss the general framework of the VPA model in comparison to other environmental and genetic ASD models.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"260-289"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49689184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.","authors":"Guangcheng Zhong, Xinyue Wang, Jiaqi Li, Zhouyuan Xie, Qiqing Wu, Jiaxin Chen, Yiyun Wang, Ziying Chen, Xinyue Cao, Tianyao Li, Jinman Liu, Qi Wang","doi":"10.2174/1570159X22666231103085859","DOIUrl":"10.2174/1570159X22666231103085859","url":null,"abstract":"<p><p>Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1650-1671"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of Alzheimer's Disease and Depression.","authors":"Sixin Li, Qian Zhang, Jian Liu, Nan Zhang, Xinyu Li, Ying Liu, Huiwen Qiu, Jing Li, Hui Cao","doi":"10.2174/1570159X22666240730154834","DOIUrl":"10.2174/1570159X22666240730154834","url":null,"abstract":"<p><strong>Background: </strong>The link between Alzheimer's disease and depression has been confirmed by clinical and epidemiological research. Therefore, our study examined the literary landscape and prevalent themes in depression-related research works on Alzheimer's disease through bibliometric analysis.</p><p><strong>Methods: </strong>Relevant literature was identified from the Web of Science core collection. Bibliometric parameters were extracted, and the major contributors were defined in terms of countries, institutions, authors, and articles using Microsoft Excel 2019 and VOSviewer. VOSviewer and CiteSpace were employed to visualize the scientific networks and seminal topics.</p><p><strong>Results: </strong>The analysis of literature utilised 10,553 articles published from 1991 until 2023. The three countries or regions with the most publications were spread across the United States, China, and England. The University of Toronto and the University of Pittsburgh were the major contributors to the institutions. Lyketsos, Constantine G., Cummings, JL were found to make outstanding contributions. Journal of Alzheimer's Disease was identified as the most productive journal. Furthermore, \"Alzheimer's\", \"depression\", \"dementia\", and \"mild cognitive decline\" were the main topics of discussion during this period.</p><p><strong>Limitations: </strong>Data were searched from a single database to become compatible with VOSviewer and CiteSpace, leading to a selection bias. Manuscripts in English were considered, leading to a language bias.</p><p><strong>Conclusion: </strong>Articles on \"Alzheimer's\" and \"depression\" displayed an upward trend. The prevalent themes addressed were the mechanisms of depression-associated Alzheimer's disease, the identification of depression and cognitive decline in the early stages of Alzheimer's, alleviating depression and improving life quality in Alzheimer's patients and their caregivers, and diagnosing and treating neuropsychiatric symptoms in Alzheimer. Future research on these hot topics would promote understanding in this field.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"98-115"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch Signaling in Central Nervous System: From Cellular Development to Multiple Sclerosis Disease.","authors":"Hamid Askari, Fatemeh Rabiei, Masoomeh Yahyazadeh, Giuseppe Biagini, Maryam Ghasemi-Kasman","doi":"10.2174/1570159X22666240731114906","DOIUrl":"10.2174/1570159X22666240731114906","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Multiple sclerosis (MS), is characterized by autoimmune-driven neuroinflammation, axonal degeneration, and demyelination. This study aimed to explore the therapeutic potential of targeting Notch signaling within the central nervous system (CNS) in the context of MS. Understanding the intricate roles of Notch signaling could pave the way for targeted interventions to mitigate MS progression.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using databases such as PubMed, Web of Science, and Scopus. Keywords such as \"Notch signaling,\" \"neuroglial interactions,\" and \"MS\" were used. The selection criteria included relevance to neuroglial interactions, peer-reviewed publications, and studies involving animal models of MS.</p><p><strong>Results: </strong>This review highlights the diverse functions of Notch signaling in CNS development, including its regulation of neural stem cell differentiation into neurons, astrocytes, and oligodendrocytes. In the context of MS, Notch signaling has emerged as a promising therapeutic target, exhibiting positive impacts on neuroprotection and remyelination. However, its intricate nature within the CNS necessitates precise modulation for therapeutic efficacy.</p><p><strong>Conclusion: </strong>This study provides a comprehensive overview of the potential therapeutic role of Notch signaling in MS. The findings underscore the significance of Notch modulation for neuroprotection and remyelination, emphasizing the need for precision in therapeutic interventions. Further research is imperative to elucidate the specific underlying mechanisms involved, which will provide a foundation for targeted therapeutic strategies for the management of MS and related neurodegenerative disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"3-19"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Natural Protoalkaloid Methyl-2-Amino-3-Methoxybenzoate (MAM) Alleviates Positive as well as Cognitive Symptoms in Rat and Mouse Schizophrenia Models.","authors":"Yami Bright, Dorien A Maas, Michel M M Verheij, Maria S Paladini, Helene I V Amatdjais-Groenen, Raffaella Molteni, Marco A Riva, Gerard J M Martens, Judith R Homberg","doi":"10.2174/1570159X21666230720122354","DOIUrl":"10.2174/1570159X21666230720122354","url":null,"abstract":"<p><p>The development of new antipsychotics with pro-cognitive properties and less side effects represents a priority in schizophrenia drug research. In this study, we present for the first time a preclinical exploration of the effects of the promising natural atypical antipsychotic Methyl-2-Amino-3- Methoxybenzoate (MAM), a brain-penetrable protoalkaloid from the seed of the plant Nigella damascena. Using animal models related to hyperdopaminergic activity, namely the pharmacogenetic apomorphine (D2/D1 receptor agonist)-susceptible (APO-SUS) rat model and pharmacologically induced mouse and rat models of schizophrenia, we found that MAM reduced gnawing stereotypy and climbing behaviours induced by dopaminergic agents. This predicts antipsychotic activity. In line, MAM antagonized apomorphine-induced c-Fos and NPAS4 mRNA levels in post-mortem brain nucleus accumbens and dorsolateral striatum of APO-SUS rats. Furthermore, phencyclidine (PCP, an NMDA receptor antagonist) and 2,5-Dimethoxy-4-iodoamphetamine (DOI, a 5HT2A/2C receptor agonist) induced prepulse inhibition deficits, reflecting the positive symptoms of schizophrenia, which were rescued by treatment with MAM and atypical antipsychotics alike. Post-mortem brain immunostaining revealed that MAM blocked the strong activation of both PCP- and DOI-induced c-Fos immunoreactivity in a number of cortical areas. Finally, during a 28-day subchronic treatment regime, MAM did not induce weight gain, hyperglycemia, hyperlipidemia or hepato- and nephrotoxic effects, side effects known to be induced by atypical antipsychotics. MAM also did not show any cataleptic effects. In conclusion, its brain penetrability, the apparent absence of preclinical side effects, and its ability to antagonize positive and cognitive symptoms associated with schizophrenia make MAM an exciting new antipsychotic drug that deserves clinical testing.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"323-338"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}