{"title":"New Insights Into Pharmacology of GABAA Receptor Alpha Subunits-Selective Modulators.","authors":"Miruna Valeria Moraru, Smaranda Stoleru, Aurelian Zugravu, Oana Andreia Coman, Ion Fulga","doi":"10.1097/MJT.0000000000001810","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001810","url":null,"abstract":"<p><strong>Background: </strong>Benzodiazepines have long held a leading position in medical therapeutics, known for their multiple common therapeutic properties and primarily being prescribed for anxiety and insomnia. However, their lack of specificity and various side effects have led to a reevaluation of their long-term use, resulting in a rapid growth in the literature focusing on targeted therapies.</p><p><strong>Areas of uncertainty: </strong>Despite many efforts, uncertainties persist and there are heterogeneous findings across studies regarding the pharmacological effects attributed to gamma-aminobutyric acid type A (GABAA) receptor subunits. Selective compounds targeting GABAA receptor alpha subunits are currently under active research and definitive conclusions have not been reached yet. Some compounds have not progressed to clinical trials, while others, if advanced, have been halted. These challenges emphasize the difficulty in translating preclinical findings into clinical use.</p><p><strong>Data sources: </strong>A literature review was conducted using the PubMed database, searching for articles discussing GABAA receptor subunits. The search was refined by including only selective compounds with potential anxiolytic and cognitive enhancement properties.</p><p><strong>Results: </strong>Findings reveal compounds with promising anxiolytic and antidepressant effects with minimal sedation and absence of tolerance development. Moreover, some compounds show potential in alleviating cognitive dysfunction. There is a broad spectrum of potential therapeutic applications for selective compounds, ranging from neurological disorders such as epilepsy and neuropathic pain to cognitive dysfunction-related conditions. Currently, the leading selective compounds with the most promising results in ongoing clinical trials are basmisanil and darigabat. Basmisanil holds further exploration potential in the treatment of cognitive impairment and related conditions, while darigabat shows progress in the advancement of adjunctive therapy of focal onset seizures and for the treatment of panic disorder, respectively.</p><p><strong>Conclusions: </strong>Future drug discovery efforts are encouraged to focus on positive allosteric modulators that selectively target the α2, α3 subunits and negative/positive allosteric modulators that target the α5 subunit of the GABAA receptor. The pursuit of ligands possessing only anxiolytic effects or those enhancing cognition continues to be an important focus for future research, with promising advancements depicted in recent studies.</p>","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Study on Periorbital Edema Following Postcollagen Injection.","authors":"Huinan Chang, Leilei Guo","doi":"10.1097/MJT.0000000000001793","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001793","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fouad Jaber, Mohammed Ayyad, Saqr Alsakarneh, Tala Alsharaeh, Ahmed-Jordan Salahat, Mohammad Jaber, Manesh Kumar Gangwani, Yazan Abboud, Islam Mohamed, Hassam Ali, Yassine Kilani, Francis A Farraye, Jana G Hashash
{"title":"Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review Ad Meta-Analysis of Randomized Controlled Trials.","authors":"Fouad Jaber, Mohammed Ayyad, Saqr Alsakarneh, Tala Alsharaeh, Ahmed-Jordan Salahat, Mohammad Jaber, Manesh Kumar Gangwani, Yazan Abboud, Islam Mohamed, Hassam Ali, Yassine Kilani, Francis A Farraye, Jana G Hashash","doi":"10.1097/MJT.0000000000001766","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001766","url":null,"abstract":"<p><strong>Background: </strong>Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).</p><p><strong>Study question: </strong>What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?</p><p><strong>Data sources: </strong>MEDLINE, Embase, Scopus, and Cochrane databases.</p><p><strong>Study design: </strong>A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.</p><p><strong>Results: </strong>In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].</p><p><strong>Conclusion: </strong>Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.</p>","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Eosinophil-Related Disorders With Myelitis as the Predominant Clinical Manifestation: A Case Report.","authors":"Min-Hui Shen, Ji-Hong Jiang, Cong-Ying Xu","doi":"10.1097/MJT.0000000000001789","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001789","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard Isralowitz, Patricia A Findley, Alexander Reznik
{"title":"Attitudes and Knowledge of Medical Students in South of Israel Toward Medical Cannabis.","authors":"Richard Isralowitz, Patricia A Findley, Alexander Reznik","doi":"10.1097/MJT.0000000000001821","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001821","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Tanashat, Osama Bisht, Mohamed Abuelazm, Obieda Altobaishat, Ubaid Khan, Mohamed Abouzid
{"title":"Transthyretin Stabilizers Treatment in Patients With Transthyretin-Mediated Cardiac Amyloidosis: A Systematic Review and Meta-Analysis.","authors":"Mohammad Tanashat, Osama Bisht, Mohamed Abuelazm, Obieda Altobaishat, Ubaid Khan, Mohamed Abouzid","doi":"10.1097/MJT.0000000000001799","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001799","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sai Spoorthy Penumarthi, Bhavani Lalkota, Shivani Jangili, Shruthi Salla, Santhosh Reddy Satti, Shantan Venishetty, Manasa Alla, Sowmya Iyengar, Mithun Sharma, P N Rao, D Nageshwar Reddy, Anand V Kulkarni
{"title":"Short-Term Primary Rifaximin Prophylaxis Has No Beneficial Role in Patients With Cirrhosis.","authors":"Sai Spoorthy Penumarthi, Bhavani Lalkota, Shivani Jangili, Shruthi Salla, Santhosh Reddy Satti, Shantan Venishetty, Manasa Alla, Sowmya Iyengar, Mithun Sharma, P N Rao, D Nageshwar Reddy, Anand V Kulkarni","doi":"10.1097/MJT.0000000000001802","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001802","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Li, Yong-Ping Chen, Ya He, Min Wang, Sheng-Li Chen, Li-Na Zhang
{"title":"Impact of L-PGDS Suppression on Cerebral Ischemia/Reperfusion Injury Through the PPARγ/AMPK/mTOR Pathway: Clinical Implications for Therapeutic Intervention.","authors":"Li Li, Yong-Ping Chen, Ya He, Min Wang, Sheng-Li Chen, Li-Na Zhang","doi":"10.1097/MJT.0000000000001801","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001801","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Audra Boscoe, Rebecca McCracken, Punit Marathe, Kareem Osman
{"title":"Response to Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.","authors":"Audra Boscoe, Rebecca McCracken, Punit Marathe, Kareem Osman","doi":"10.1097/MJT.0000000000001786","DOIUrl":"https://doi.org/10.1097/MJT.0000000000001786","url":null,"abstract":"","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}