The
gamma-aminobutyric acid type B (GABAB) receptor agonist, the
sodium salt of
gamma-hydroxybutyrate (GHB), significantly improved
pain, sleep disturbance and
fatigue in
fibromyalgia (FM) patients. However, the use of GABAB receptor agonists is limited by their undesirable side-effects. To clarify whether GABAB receptor positive allosteric modulator (PAM) approach would achieve
analgesia with less side-effects than GABAB receptor agonist in FM, we investigated the potential of a novel GABAB receptor PAM,
ASP8062, for FM treatment. We examined the in vitro profiles of
ASP8062, the effects of a GABAB receptor PAM and an agonist on
pain in a rat model of FM, and the sleep/wake cycle, EEG during sleep stages and motor coordination in rats.
ASP8062 showed PAM activity on human and rat GABAB receptors.
Oral administration of
ASP8062 significantly reversed the decrease in muscle pressure threshold in
reserpine-induced
myalgia rats. The
analgesic effects of
ASP8062 were significantly blocked by a GABAB receptor antagonist.
ASP8062 had a significant effect on motor coordination at a 1000-fold higher dose than the
analgesic dose in rats.
ASP8062 significantly decreased total REM sleep time and frequency of sleep interruptions, and increased the power in delta waves frequency during non-REM sleep in rats.
ASP8062, a novel GABAB receptor PAM, has therapeutic potential to exert
analgesic effects with less side-effects compared to GABAB receptor agonists in patients with FM.