Fadolmidine - Favourable adverse effects profile for spinal analgesia suggested by in vitro and in vivo models.

Fadolmidine - Favourable adverse effects profile for spinal analgesia suggested by in vitro and in vivo models. Eur J Pharmacol. 2020 Jun 24;:173296 Authors: Leino T, Lehtimäki J, Koivisto A, Haapalinna A, Pesonen U Abstract Fadolmidine is an α2-adrenoceptor full agonist developed for spinal analgesia with a local mode of action. The purpose of this study was to demonstrate the safety of fadolmidine on known α2-adrenoceptor-related effects: kidney function, urodynamics and cardiovascular variables. Furthermore, the binding affinity of fadolmidine for the 5-HT3 receptor prompted functional studies on 5-HT3. According to the binding affinity data, fadolmidine demonstrated partial agonism on the 5-HT3 receptor in transfected cells and in guinea pig ileum preparation. However, intravenous (IV) fadolmidine did not produce any 5-HT3-related hemodynamic effects in anaesthetised rats. In urodynamic studies, intrathecal (IT) fadolmidine interrupted volume-evoked voiding cycles and induced overflow incontinence at high concentrations in anaesthetised rats; however, at the analgesic dose range, the effects were mild. The effects of fadolmidine on kidney function were studied in conscious rats after IV and IT dosing. While IT fadolmidine increased dose-dependent urine output, sodium ion concentration, IV doses increased only sodium ion concentration The effects of IT fadolmidine on heart rate (HR), mean arterial pressure (MAP) and sedation we...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research