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Synthesis, Anticonvulsant, Antinociceptive Activity and Preliminary Safety Evaluations of Novel Hybrid Imidazolidine-2,4-Dione Derivatives with Morpholine Moiety.
ChemMedChem
December 2024
Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland.
This study aimed to design new hybrid compounds with imidazolidin-2,4-dione and morpholine rings as broad spectrum anticonvulsants. To achieve this goal, all compounds were evaluated in animal seizure models, namely the maximal electroshock (MES), the subcutaneous pentylenetetrazole (scPTZ), and selected in the 6 Hz (32 mA) tests. The most promising compound, 5-isopropyl-3-(morpholinomethyl)-5-phenylimidazolidine-2,4-dione (19), demonstrated broader anticonvulsant activity than phenytoin or levetiracetam, with ED of 26.
View Article and Find Full Text PDFStrategies to innovate emergency care of status epilepticus.
Neurotherapeutics
December 2024
Department of Neurology and Neuroscience Brain Institute University of Virginia, School of Medicine, Health Sciences Center, Box 801330, Charlottesville, VA 22908-1330, USA. Electronic address:
Generalized Convulsive status epilepticus (SE) is a neurological emergency because prolonged convulsions can cause respiratory compromise and neuronal injury. Compromised GABA-mediated inhibition is a defining feature of SE, and many current therapies are benzodiazepines, which are allosteric modulators of GABA-A receptors. Many patients with medically refractory epilepsy are at risk for SE.
View Article and Find Full Text PDFBottom-up PBPK modeling of phenytoin brain disposition in postpartum newborns after intrauterine dosing.
Drug Metab Pers Ther
September 2024
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science & Technology, Irbid, Jordan.
Article Synopsis
- * Researchers used a physiologically based pharmacokinetic (PBPK) model to estimate the levels of phenytoin in newborns, focusing on its concentrations in brain extracellular fluid, plasma, and saliva.
- * Findings indicated that phenytoin levels in the newborns were below harmful thresholds, suggesting that monitoring salivary levels could be a safer method to prevent brain toxicity in infants born to mothers on this medication, though more research is needed on dosing for infants.
Case report and literature review: management of Paxlovid (nirmatrelvir/ritonavir)-induced acute tacrolimus toxicity in a patient with systemic lupus erythematosus.
Front Pharmacol
June 2024
Department of Emergency Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Article Synopsis
- * A 32-year-old male experienced acute nephrotoxicity and neurotoxicity after resuming Tacrolimus following NMV/r treatment, highlighting the inhibitory effects of ritonavir on liver enzymes and drug transporters.
- * This case illustrates the need for vigilance regarding DDIs, the importance of pharmacist involvement in treatment decisions, and suggests the potential for personalized therapy in managing COVID-19 in patients with compromised immune systems.
Clinical pharmacology considerations and drug-drug interactions with long-acting cabotegravir and rilpivirine relevant to sub-Saharan Africa.
Br J Clin Pharmacol
September 2024
MRC/UVRI-LSHTM Uganda Research Unit, Entebbe, Uganda.
Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug-drug interactions (DDIs) with frequent concomitant medications in African settings.
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