Affinity, maximal effect and concentration sensitivity can lead to different selectivity descriptions.
Two triazolam analogues underwent receptor binding, patch-clamp, monkey behavior and docking studies. Binding assays did not show the intended subtype selectivity. One analogue nevertheless showed a substantial functional-potency difference between tested receptor configurations; sedative and motor effects still occurred in behavioral work.
Engineered receptors and preclinical behavior do not establish human therapeutic advantage. A functional-potency ratio does not imply absence of effects at other subtypes, and docking does not replace experimentally measured action.
For discussing a new benzodiazepine, state which assay supports the word selective. Distinguish potency from maximal potentiation and from the dose separating desired and unwanted behavior. The study illustrates why a single receptor ratio cannot establish freedom from sedation or a superior clinical safety margin.
Source: Publication PMC8094182. Applications to expert review are interpretive analysis.
Related reading: Bromazepam Electrode Study Tested Degradation Selectivity in a Pharmaceutical Assay.