Nonopioid and neuropathy-specific analgesic action
of the nootropic drug nefiracetam in mice

by
Rashid MH, Ueda H.
Division of Molecular Pharmacology and Neuroscience,
Nagasaki University Graduate School of Biomedical Sciences, Japan.
J Pharmacol Exp Ther 2002 Oct;303(1):226-31


ABSTRACT

Nootropic drug nefiracetam and related compounds are used in diseases with learning and memory deficits. Recent studies have implicated relationships between learning, memory, and chronic pain. Thus, in the present report, we have studied the effects of nootropic drug nefiracetam on the thermal and mechanical hyperalgesia induced by partial sciatic nerve ligation or streptozotocin treatment in mice. In the thermal paw withdrawal test, p.o., s.c., i.t., and i.c.v. administration of nefiracetam dose dependently reversed the thermal hyperalgesia observed in nerve-injured mice. Nefiracetam (p.o. and i.t.) also significantly reversed the thermal hyperalgesia observed in streptozotocin-induced diabetic mice. In the paw pressure test, p.o. and i.t. administration of nefiracetam dose dependently reversed the mechanical hyperalgesia observed in both nerve-injured and diabetic mice. In contrast, nefiracetam had no effect in sham-operated or control nondiabetic mice in all paradigms. Among other pyrrolidine nootropics (p.o.), aniracetam produced significant analgesic effects. Other analogs also had some, but not significant, analgesic effects. Finally, nefiracetam (p.o.)-induced analgesia in injured mice was not affected by opioid antagonist naloxone (s.c., i.t., and i.c.v.) but was dose dependently inhibited by nicotinic antagonist mecamylamine (i.t. and i.c.v.). The analgesic effect of i.t. nefiracetam was also blocked by i.t. mecamylamine pretreatment. Together, these findings suggest that nefiracetam, a new member of the piracetam group of cognition enhancers, could be a good therapeutic tool against neuropathic pain. We also demonstrate that nefiracetam-induced analgesic action was nonopioid in nature and was due to stimulation of nicotinic cholinergic system at spinal and supraspinal levels.
Piracetam
Nootropics
Aniracetam
Oxiracetam
Nefiracetam
Cholinergics
Galantamine
Acetylcholine
Neurosteroids
Pramiracetam
Nootropics ('smart drugs')


Refs
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Critique of Huxley's Brave New World

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