Cited by 34Fibromyalgia and Chronic Fatigue Syndrome ResearchPain Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research

A novel GABAB receptor positive allosteric modulator, ASP8062, exerts analgesic effects in a rat model of fibromyalgia

Murai, Nobuhito, Kondo, Yuji, Akuzawa, Shinobu, Mihara, Takuma, Shiraishi, Nobuyuki, Kakimoto, Shuichiro, Matsumoto, Mitsuyuki·2019·European Journal of Pharmacology

Abstract

The gamma-aminobutyric acid type B (GABA B) receptor agonist, the sodium salt of gamma-hydroxybutyrate (GHB), significantly improved pain, sleep disturbance and fatigue in fibromyalgia (FM) patients. However, the use of GABA B receptor agonists is limited by their undesirable side-effects. To clarify whether GABA B receptor positive allosteric modulator (PAM) approach would achieve analgesia with less side-effects than GABA B receptor agonist in FM, we investigated the potential of a novel GABA B receptor PAM, ASP8062, for FM treatment. We examined the in vitro profiles of ASP8062, the effects of a GABA B 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 GABA B 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 GABA B 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 GABA B receptor PAM, has therapeutic potential to exert analgesic effects with less side-effects compared to GABA B receptor agonists in patients with FM.

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Crossref · 10.1016/j.ejphar.2019.172750

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  • In an animal study comparing ASP8062 and baclofen in male and female rats, both compounds reduced alcohol consumption in both genders, with ASP8062 more effective in males and baclofen having a greater impact on females.

    “In a recent animal study comparing ASP8062 and baclofen in male and female rats to evaluate their effects on alcohol self-administration, both compounds demonstrated a reduction in alcohol consumption in both genders. Notably, ASP8062 was more effective in males, while baclofen had a greater impact on females.”

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Authors
Murai, N., Kondo, Y., Akuzawa, S., Mihara, T., Shiraishi, N., Kakimoto, S., & Matsumoto, M.
Affiliations
Astellas Pharma (Japan) (JP)
Corresponding author
Murai, Nobuhito
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2019-12
Volume
865
Pages
172750
ISSN
0014-2999 (ISSN-L)
OpenAlex
W2982110959
Cited by
34
References
42
Citations by year
2026: 7 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 5
FWCI
2.58
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Astellas Pharma
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
GABAB receptors, positive allosteric modulators, fibromyalgia, analgesia, sleep disorders, REM sleep, delta oscillations, motor coordination, GABA-B receptor agonist, gamma-hydroxybutyric acid
MeSH terms
Allosteric Regulation, Analgesics, Animals, Calcium, Disease Models, Animal, Electroencephalography, Fibromyalgia, gamma-Aminobutyric Acid, Humans, Male, Morpholines, Pyrimidines, Reserpine, Sleep, Rats, Sprague-Dawley, Receptors, GABA-B, Muscle, Skeletal, HEK293 Cells, Myalgia

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