Pharmacology & Therapeutics最新文献

{"title":"TAAR1 as an emerging target for the treatment of psychiatric disorders","authors":"Jianfeng Liu ,&nbsp;Ruyan Wu ,&nbsp;Jun-Xu Li","doi":"10.1016/j.pharmthera.2023.108580","DOIUrl":"10.1016/j.pharmthera.2023.108580","url":null,"abstract":"<div><p>Trace amines, a group of amines expressed at the nanomolar level in the mammalian brain, can modulate monoamine<span> transmission. The discovery of and the functional research on the trace amine-associated receptors (TAARs), especially the most well-characterized TAAR1, have largely facilitated our understanding of the function of the trace amine system in the brain. TAAR1 is expressed in the mammalian brain at a low level and widely distributed in the monoaminergic system, including the ventral tegmental area and substantial nigra, where the dopamine neurons reside in the mammalian brain. Growing in vitro and in vivo evidence has demonstrated that TAAR1 could negatively modulate monoamine transmission and play a crucial role in many psychiatric disorders, including schizophrenia, substance use disorders, sleep disorders, depression, and anxiety. Notably, in the last two decades, many studies have repeatedly confirmed the pharmacological effects of the selective TAAR1 ligands in various preclinical models of psychiatric disorders. Recent clinical trials<span> of the dual TAAR1 and serotonin receptor agonist ulotaront also revealed a potential efficacy for treating schizophrenia. Here, we review the current understanding of the TAAR1 system and the recent advances in the elucidation of behavioral and physiological properties of TAAR1 agonists evaluated both in preclinical animal models and clinical trials. We also discuss the potential TAAR1-dependent signaling pathways and the cellular mechanisms underlying the inhibitory effects of TAAR1 activation on drug addiction. We conclude that TAAR1 is an emerging target for the treatment of psychiatric disorders.</span></span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108580"},"PeriodicalIF":13.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139014759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets","authors":"Alia Mushtaq ,&nbsp;Peng Wu ,&nbsp;Muhammad Moazzam Naseer","doi":"10.1016/j.pharmthera.2023.108579","DOIUrl":"10.1016/j.pharmthera.2023.108579","url":null,"abstract":"<div><p><span><span><span>Cancer, a noncommunicable disease, is the leading cause of mortality worldwide and is anticipated to rise by 75% in the next two decades, reaching approximately 25 million cases. Traditional cancer treatments, such as radiotherapy and surgery, have shown limited success in reducing cancer incidence. As a result, the focus of </span>cancer chemotherapy has switched to the development of novel small molecule </span>antitumor agents as an alternate strategy for combating and managing cancer rates. </span>Heterocyclic compounds<span> are such agents that bind to specific residues in target proteins, inhibiting their function and potentially providing cancer treatment. This review focuses on privileged heterocyclic pharmacophores with potent activity against carbonic anhydrases<span><span> and kinases, which are important anticancer targets. Evaluation of ongoing pre-clinical and clinical research of heterocyclic compounds with potential therapeutic value against a variety of malignancies as well as the provision of a concise summary of the role of heterocyclic scaffolds in various chemotherapy protocols have also been discussed. The main objective of the article is to highlight key heterocyclic scaffolds involved in recent anticancer drug design that demands further attention from the </span>drug development community to find more effective and safer targeted small-molecule anticancer agents.</span></span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"254 ","pages":"Article 108579"},"PeriodicalIF":13.5,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139061068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases","authors":"Takuma Isshiki ,&nbsp;Safaa Naiel ,&nbsp;Megan Vierhout ,&nbsp;Kohei Otsubo ,&nbsp;Pareesa Ali ,&nbsp;Kazuya Tsubouchi ,&nbsp;Parichehr Yazdanshenas ,&nbsp;Vaishnavi Kumaran ,&nbsp;Anna Dvorkin-Gheva ,&nbsp;Martin R.J. Kolb ,&nbsp;Kjetil Ask","doi":"10.1016/j.pharmthera.2023.108578","DOIUrl":"10.1016/j.pharmthera.2023.108578","url":null,"abstract":"<div><p><span><span>The treatment of interstitial lung diseases, including </span>idiopathic pulmonary fibrosis<span><span><span> (IPF), remains challenging as current available antifibrotic agents are not effective in halting </span>disease progression. </span>Connective tissue growth factor<span> (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the </span></span></span>CCN family of proteins<span><span> that regulates cell signaling through cell surface receptors<span> such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting </span></span>lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108578"},"PeriodicalIF":13.5,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138635775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic cation transporters in psychiatric and substance use disorders","authors":"Lauren E. Honan ,&nbsp;Rheaclare Fraser-Spears ,&nbsp;Lynette C. Daws","doi":"10.1016/j.pharmthera.2023.108574","DOIUrl":"10.1016/j.pharmthera.2023.108574","url":null,"abstract":"<div><p>Psychiatric and substance use disorders inflict major public health burdens worldwide. Their widespread burden is compounded by a dearth of effective treatments, underscoring a dire need to uncover novel therapeutic targets. In this review, we summarize the literature implicating organic cation transporters (OCTs), including three subtypes of OCTs (OCT1, OCT2, and OCT3) and the plasma membrane monoamine transporter (PMAT), in the neurobiology of psychiatric and substance use disorders with an emphasis on mood and anxiety disorders, alcohol use disorder, and psychostimulant use disorder. OCTs transport monoamines with a low affinity but high capacity, situating them to play a central role in regulating monoamine homeostasis. Preclinical evidence discussed here suggests that OCTs may serve as promising targets for treatment of psychiatric and substance use disorders and encourage future research into their therapeutic potential.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108574"},"PeriodicalIF":13.5,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725823002383/pdfft?md5=ae9d3e8e6f5cdaedb2e576b776f77db5&pid=1-s2.0-S0163725823002383-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical advances in TNC delivery vectors and their conjugate agents","authors":"Wujun Chen ,&nbsp;Yudong Wu ,&nbsp;Jie Wang ,&nbsp;Wanpeng Yu ,&nbsp;Xin Shen ,&nbsp;Kai Zhao ,&nbsp;Bing Liang ,&nbsp;Xiaokun Hu ,&nbsp;Shuai Wang ,&nbsp;Hongfei Jiang ,&nbsp;Xinlin Liu ,&nbsp;Miao Zhang ,&nbsp;Xiaohui Xing ,&nbsp;Chao Wang ,&nbsp;Dongming Xing","doi":"10.1016/j.pharmthera.2023.108577","DOIUrl":"10.1016/j.pharmthera.2023.108577","url":null,"abstract":"<div><p><span><span>Tenascin<span><span> C (TNC), a glycoprotein<span> that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers<span>, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, </span></span></span>G11<span>, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine–glycine–aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody–drug conjugates (ADCs), antibody fragment–drug conjugates (FDCs), immune-stimulating </span></span></span>antibody conjugates (ISACs), and radionuclide–drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include </span>¹¹¹In-DTPA-BC-2, ¹³¹I-BC-2, ¹³¹I-BC-4, ⁹⁰Y-BC4, ¹³¹I<img>81C6, ¹³¹I-ch81C6, ²¹¹At-ch81C6, F16<img>¹²⁴I, ¹³¹I-tenatumomab, ST2146biot, FDC ¹³¹I-F16S1PF(ab’)2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and ¹²⁵<span>I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108577"},"PeriodicalIF":13.5,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases","authors":"Yigan Zhang ,&nbsp;Yumei Lei ,&nbsp;Yanbin Dong ,&nbsp;Shuwen Chen ,&nbsp;Siyuan Sun ,&nbsp;Fange Zhou ,&nbsp;Zhiwen Zhao ,&nbsp;Bonan Chen ,&nbsp;Lv Wei ,&nbsp;Juan Chen ,&nbsp;Zhongji Meng","doi":"10.1016/j.pharmthera.2023.108576","DOIUrl":"10.1016/j.pharmthera.2023.108576","url":null,"abstract":"<div><p><span>RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification on mRNA is mediated by the classical </span><em>N</em>-acetyltransferase NAT10. Subsequent studies have underscored the essential implications of NAT10 and mRNA ac4C modification across both physiological and pathological regulatory processes. In this review, we aimed to explore the discovery history of RNA ac4C modification, its detection methods, and its regulatory mechanisms in disease and physiological development. We offer a forward-looking examination and discourse concerning the employment of RNA ac4C modification as a prospective therapeutic strategy across diverse diseases. Furthermore, we comprehensively summarize the functions and mechanisms of NAT10 in gene expression regulation and pathogenesis independent of RNA ac4C modification.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108576"},"PeriodicalIF":13.5,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138551238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension & dementia: Pathophysiology & potential utility of antihypertensives in reducing disease burden","authors":"Mara Lyon ,&nbsp;Josie L. Fullerton ,&nbsp;Simon Kennedy,&nbsp;Lorraine M. Work","doi":"10.1016/j.pharmthera.2023.108575","DOIUrl":"10.1016/j.pharmthera.2023.108575","url":null,"abstract":"<div><p>Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it is of major importance to identify new ways to reduce its prevalence. Hypertension is recognised as a modifiable risk factor for dementia, particularly for the two most common subtypes; vascular dementia (VaD) and Alzheimer's disease (AD). From the current literature, identified through a comprehensive literature search of PubMed and Cochrane Library, this review aims to establish the stage in adulthood when hypertension becomes a risk for cognitive decline and dementia, and whether antihypertensive treatment is effective as a preventative therapy.</p><p>Observational studies generally found hypertension in mid-life (age 45-64) to be correlated with an increased risk of cognitive decline and dementia incidence, including both VaD and AD. Hypertension manifesting in late life (age <span><math><mo>≥</mo></math></span> 65) was demonstrated to be less of a risk, to the extent that incidences of high blood pressure (BP) in the very elderly (age <span><math><mo>≥</mo></math></span> 75) may even be related to reduced incidence of dementias. Despite the evidence linking hypertension to dementia, there were conflicting findings as to whether the use of antihypertensives was beneficial for its prevention and this conflicting evidence and inconsistent results could be due to the methodological differences between the reviewed observational and randomised controlled trials. Furthermore, dihydropyridine calcium channel blockers and potassium-sparing diuretics were proposed to have neuroprotective properties in addition to BP lowering. Overall, if antihypertensives are confirmed to be beneficial by larger-scale homogenous trials with longer follow-up durations, treatment of hypertension, particularly in mid-life, could be an effective strategy to considerably lower the prevalence of dementia. Furthermore, greater clarification of the neuroprotective properties that some antihypertensives possess will allow for better clinical practice guidance on the choice of antihypertensive class for both BP lowering and dementia prevention.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108575"},"PeriodicalIF":13.5,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725823002395/pdfft?md5=25bfb7a8c214f3f10b8efa8bab78cc40&pid=1-s2.0-S0163725823002395-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of pexidartinib for microglia depletion and renewal","authors":"Marc-Philipp Weyer ,&nbsp;Jenny Strehle ,&nbsp;Michael K.E. Schäfer ,&nbsp;Irmgard Tegeder","doi":"10.1016/j.pharmthera.2023.108565","DOIUrl":"10.1016/j.pharmthera.2023.108565","url":null,"abstract":"<div><p><span>Pexidartinib (PLX3397) is a small molecule </span>receptor tyrosine kinase<span><span><span><span> inhibitor of colony stimulating factor 1 receptor (CSF1R) with moderate selectivity over other members of the </span>platelet derived growth factor receptor family. It is approved for treatment of tenosynovial giant cell tumors (TGCT). CSF1R is highly expressed by microglia, which are macrophages of the central nervous system (CNS) that defend the CNS against injury and pathogens and contribute to synapse development and plasticity. Challenged by pathogens, apoptotic cells, debris, or inflammatory molecules they adopt a responsive state to propagate the inflammation and eventually return to a homeostatic state. The phenotypic switch may fail, and disease-associated microglia contribute to the </span>pathophysiology<span><span> in neurodegenerative or neuropsychiatric diseases or long-lasting detrimental brain inflammation after brain, spinal cord or nerve injury or ischemia/hemorrhage. Microglia also contribute to the growth permissive tumor microenvironment of </span>glioblastoma (GBM). In rodents, continuous treatment for 1–2 weeks via pexidartinib food pellets leads to a depletion of microglia and subsequent repopulation from the remaining fraction, which is aided by peripheral monocytes that search empty niches for engraftment. The putative therapeutic benefit of such microglia depletion or forced renewal has been assessed in almost any rodent model of </span></span>CNS disease or injury or GBM with heterogeneous outcomes, but a tendency of partial beneficial effects. So far, microglia monitoring e.g. via positron emission imaging is not standard of care for patients receiving Pexidartinib (e.g. for TGCT), so that the depletion and repopulation efficiency in humans is still largely unknown. Considering the virtuous functions of microglia, continuous depletion is likely no therapeutic option but short-lasting transient partial depletion to stimulate microglia renewal or replace microglia in genetic disease in combination with e.g. stem cell transplantation or as part of a multimodal concept in treatment of glioblastoma appears feasible. The present review provides an overview of the preclinical evidence pro and contra microglia depletion as a therapeutic approach.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108565"},"PeriodicalIF":13.5,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges","authors":"Poonam Yadav ,&nbsp;Sumeet Kumar Singh ,&nbsp;Sonu Rajput ,&nbsp;Prince Allawadhi ,&nbsp;Amit Khurana ,&nbsp;Ralf Weiskirchen ,&nbsp;Umashanker Navik","doi":"10.1016/j.pharmthera.2023.108563","DOIUrl":"10.1016/j.pharmthera.2023.108563","url":null,"abstract":"<div><p><span><span><span>The deposition of extracellular matrix and hyperplasia of connective tissue characterizes </span>chronic liver disease called </span>hepatic fibrosis<span>. Progression of hepatic fibrosis may lead to hepatocellular carcinoma. At this stage, only liver transplantation is a viable option. However, the number of possible liver donors is less than the number of patients needing transplantation. Consequently, alternative cell therapies based on non-stem cells (</span></span><em>e.g.</em>, fibroblasts, chondrocytes, keratinocytes, and hepatocytes) therapy may be able to postpone hepatic disease, but they are often ineffective. Thus, novel stem cell-based therapeutics might be potentially important cutting-edge approaches for treating liver diseases and reducing patient’ suffering. Several signaling pathways provide targets for stem cell interventions. These include pathways such as TGF-β, STAT3/BCL-2, NADPH oxidase, Raf/MEK/ERK, Notch, and Wnt/β-catenin. Moreover, mesenchymal stem cells (MSCs) stimulate interleukin (IL)-10, which inhibits T-cells and converts M1 macrophages into M2 macrophages, producing an anti-inflammatory environment. Furthermore, it inhibits the action of CD4⁺<span> and CD8</span>⁺<span> T cells and reduces the activity of TNF-α and interferon cytokines by enhancing IL-4 synthesis. Consequently, the immunomodulatory and anti-inflammatory capabilities of MSCs make them an attractive therapeutic approach. Importantly, MSCs can inhibit the activation of hepatic stellate cells, causing their apoptosis and subsequent promotion of hepatocyte proliferation, thereby replacing dead hepatocytes and reducing liver fibrosis. This review discusses the multidimensional therapeutic role of stem cells as cell-based therapeutics in liver fibrosis.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108563"},"PeriodicalIF":13.5,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138442342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retracing our steps: A review on autism research in children, its limitation and impending pharmacological interventions","authors":"Salam Salloum-Asfar,&nbsp;Nasser Zawia,&nbsp;Sara A. Abdulla","doi":"10.1016/j.pharmthera.2023.108564","DOIUrl":"10.1016/j.pharmthera.2023.108564","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction, and restricted, repetitive, and stereotypical behavior patterns. Spectrum refers to the heterogeneity of presentation, severity of symptoms, and medical comorbidities associated with ASD. Among the most common underlying medical conditions are attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, epilepsy, digestive disorders, metabolic disorders, and immune disorders. At present, in the absence of an objective and accurate diagnosis of ASD, such as a blood test, pharmacological management remains a challenge. There are no approved medications to treat the core symptoms of the disorder and behavioral interventions are typically used as first line treatment. Additionally, psychotropic drugs with different mechanisms of action have been approved to reduce associated symptoms and comorbidities, including aripiprazole, risperidone, and haloperidol for irritability and aggression, methylphenidate, atomoxetine, clonidine, and guanfacine for ADHD, and melatonin for sleep disturbances. The purpose of this review is to emphasize that it is imperative to develop objective, personalized diagnostic kits in order to tailor and individualize treatment strategies, as well as to describe the current pharmacological management options available in clinical practice and new prospects that may be helpful in managing ASD's core symptoms.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"253 ","pages":"Article 108564"},"PeriodicalIF":13.5,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725823002280/pdfft?md5=55f18ea29f4d9dcbf44be4c50427e0df&pid=1-s2.0-S0163725823002280-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}