British journal of anaesthesia
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With the increasing prevalence of children who are overweight and with obesity, anaesthesiologists must determine the optimal dosing of medications given the altered pharmacokinetics and pharmacodynamics in this population. We therefore determined the single dose of dexmedetomidine that provided sufficient sedation in 95% (ED95) of children with and without obesity as measured by a minimum Ramsay sedation score (RSS) of 4. ⋯ ChiCTR1800014266.
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Multiple cognitive and psychiatric disorders are associated with an increased tonic inhibitory conductance that is generated by α5 subunit-containing γ-aminobutyric acid type A (α5 GABAA) receptors. Negative allosteric modulators that inhibit α5 GABAA receptors (α5-NAMs) are being developed as treatments for these disorders. The effects of α5-NAMs have been studied on recombinant GABAA receptors expressed in non-neuronal cells; however, no study has compared drug effects on the tonic conductance generated by native GABAA receptors in neurones, which was the goal of this study. ⋯ Basmisanil was markedly less potent than the other α5-NAMs, an unexpected result based on studies of recombinant α5 GABAA receptors. Studying the effects of α5 GABAA receptor-selective drugs on the tonic inhibitory current in neurones could inform the selection of compounds for future clinical trials.