Apremilast regulates acute effects of ethanol and other GABAergic drugs via protein kinase A-dependent signaling.

Apremilast regulates acute effects of ethanol and other GABAergic drugs via protein kinase A-dependent signaling. Neuropharmacology. 2020 Jul 28;:108220 Authors: Blednov YA, Borghese CM, Dugan MP, Pradhan S, Thodati TM, Kichili NR, Harris RA, Messing RO Abstract Phosphodiesterase type 4 (PDE4) inhibitors prevent hydrolysis of cyclic adenosine monophosphate and increase protein kinase A (PKA)-mediated phosphorylation. PDE4 inhibitors also regulate responses to ethanol and GABAergic drugs. We investigated mechanisms by which the PDE4 inhibitor, apremilast, regulates acute effects of ethanol and GABAergic drugs in male and female mice. Apremilast prolonged the sedative-hypnotic effects of gaboxadol, zolpidem, and propofol but did not alter etomidate effects, and unexpectedly shortened the sedative-hypnotic effects of diazepam. Apremilast prolonged rotarod ataxia induced by zolpidem, propofol, and loreclezole, shortened recovery from diazepam, but had no effect on ataxia induced by gaboxadol or etomidate. The PKA inhibitor H89 blocked apremilast's ability to prolong the sedative-hypnotic effects of ethanol, gaboxadol, and propofol and to prolong ethanol- and propofol-induced ataxia. H89 also blocked apremilast's ability to shorten the sedative-hypnotic and ataxic effects of diazepam. The β1-specific antagonist, salicylidene salicylhydrazide (SCS), produced faster recovery from ethanol- and diazepam-induced ataxia, but did not alter prop...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research