Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2009.08.053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clozapine for Treatment-Resistant Disruptive Behaviors in Youths With Autism Spectrum Disorder Aged 10-17 Years: Protocol for an Open-Label Trial.
JMIR Res Protoc
January 2025
Graduate Program of Psychiatry and Behavioral Sciences, Department of Psychiatry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition emerging in early childhood, characterized by core features such as sociocommunicative deficits and repetitive, rigid behaviors, interests, and activities. In addition to these, disruptive behaviors (DB), including aggression, self-injury, and severe tantrums, are frequently observed in pediatric patients with ASD. The atypical antipsychotics risperidone and aripiprazole, currently the only Food and Drug Administration-approved treatments for severe DB in patients with ASD, often encounter therapeutic failure or intolerance.
View Article and Find Full Text PDFEstablishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Genetic Engineering, School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai 200438, China.
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named (), harboring a mutation in the - () gene. Loss of leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration.
View Article and Find Full Text PDFrecovered from hospital patients, livestock and dogs in Nigeria share near-identical genome sequences.
Microb Genom
January 2025
Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Microbial Genome Research, Braunschweig, Germany.
Genomic data on from the African continent are currently lacking, resulting in the region being under-represented in global analyses of infection (CDI) epidemiology. For the first time in Nigeria, we utilized whole-genome sequencing and phylogenetic tools to compare isolates from diarrhoeic human patients (=142), livestock (=38), poultry manure (=5) and dogs (=9) in the same geographic area (Makurdi, north-central Nigeria) and relate them to the global population. In addition, selected isolates were tested for antimicrobial susceptibility (=33) and characterized by PCR ribotyping (=53).
View Article and Find Full Text PDFSotalol poisoning and its unique treatment considerations compared with traditional therapies for beta-adrenoceptor blocking drug poisoning.
Clin Toxicol (Phila)
January 2025
Minnesota Regional Poison Center, Minneapolis, MN, USA.
Introduction: Sotalol is a beta-adrenoceptor blocking drug with unique physical and pharmacologic properties. Unlike most beta-adrenoceptor blocking drugs, sotalol is amenable to extracorporeal removal and causes QT interval prolongation and ventricular dysrhythmias. These properties have implications for treating sotalol poisoning.
View Article and Find Full Text PDFMechanisms and new advances in the efficacy of plant active ingredients in tendon-bone healing.
J Orthop Surg Res
January 2025
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, No.41 Linyin Road, Baotou, Inner Mongolia, 014010, China.
The tendon-bone interface, known as the tenosynovial union or attachment, can be easily damaged by excessive exercise or trauma. Tendon-bone healing is a significant research topic in orthopedics, encompassing various aspects of sports injuries and postoperative recovery. Surgery is the most common treatment; however, it has limited efficacy in promoting tendon-bone healing and carries a risk of postoperative recurrence, necessitating the search for more effective treatments.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!