Deprescribing Cardiovascular Medications in Older Adults Living with Frailty.

Certain medications have shown significant effectiveness in reducing the incidence of cardiovascular events and mortality, leading them to be among those that are prescribed most commonly for Canadian seniors. However, polypharmacy, which disproportionately affects older adults, is particularly concerning for frail individuals who are at higher risk for adverse medication-related events. The deprescribing process is the discontinuation, either immediate or gradual, of inappropriate medications, to address polypharmacy and improve outcomes.

Development of dual V1a/V2 antagonists containing triazolobenzazepine scaffold.

The development of a dual V1a/V2 antagonist compound is a complex and challenging task. Conivaptan is up to now the only known V1a/V2 antagonist which was approved for the treatment of euvolemic hyponatremia. Previously, we reported RGH-122, a novel selective V1a antagonist compound.

Comprehensive Diagnosis, Treatment, and Outcome of Cysticercosis in a Ring-Tailed Lemur () from a Croatian Zoo: No Longer Unusual?

is a zoonotic tapeworm of the genus that is distributed throughout the Northern Hemisphere. Wild and domestic carnivores are final hosts, while rodents and rabbits are primarily intermediate hosts, although many other mammals may harbour the larval stage, . This case report aims to describe infection in a lemur and molecularly characterise the isolated parasite.

Novel-Type GABA PAMs: Structure-Activity Relationship in Light of the Protein Structure.

Selecting a known HTS hit with the pyrazolo[1,5-]pyrimidine core, our project was started from CMPPE, and its optimization was driven by a ligand-based pharmacophore model developed on the basis of published GABA positive allosteric modulators (PAMs). Our primary goal was to improve the potency by finding new enthalpic interactions. Therefore, we included the lipophilic ligand efficiency (LLE or LipE) as an objective function in the optimization that led to a carboxylic acid derivative ().

Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist.

The V1a receptor is a major contributor in mediating the social and emotional effects of arginine-vasopressin (AVP); therefore it represents a promising target in the treatment of several neuropsychiatric conditions. The aim of this research was to design and synthesize novel and selective V1a antagonists with improved and profiles. Through optimization and detailed SAR studies, we developed low nanomolar antagonists, and further characterizations led to the discovery of the clinical candidate compound (RGH-122).