Nonopioid and Neuropathy-Specific Analgesic Action of the Nootropic Drug Nefiracetam in Mice

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 nerveinjured 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.

Increased Expression of Vanilloid Receptor 1 on Myelinated Primary Afferent Neurons Contributes to the Antihyperalgesic Effect of Capsaicin Cream in Diabetic Neuropathic Pain in Mice

“…A cut-off time of 20 s was set to prevent tissue damage. The paw pressure test was performed as described previously (Rashid and Ueda, 2002). Briefly, mice were placed into a Plexiglas chamber on a 6 ϫ 6-mm wire mesh grid floor and were allowed to accommodate for a period of 1 h. The mechanical stimulus was then delivered onto the middle of the plantar surface of the right hind paw using a transducer indicator (model 1601; IITC, Inc.).…”

“…In the present study, diabetes was induced in mice by a single i.v. injection of STZ (200 mg/kg; Wako Pure Chemicals, Richmond, VA) as reported previously (Kamei et al, 1991;Rashid and Ueda, 2002). Mice weighing ϳ30 g were injected i.v.…”

A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin

“…Racetam, even called nootropics, are a family of 2-pyrrolidinone derivatives designed in the sixties and profiled as cognition enhancers. Racetam compounds, such as nefiracetam and levetiracetam, have shown antihyperalgesic effect in animal models of neuropathic pain [37,38]. Dimiracetam itself has been already reported to be active against neuropathy induced by the chronic constriction injury of the sciatic nerve and diabetic neuropathy [39].…”

Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats

“…NEF is a novel pyrrolidone-type nootropic agent used to treat dementia associated with Alzheimer disease or secondary to cerebrovascular disorders. NEF has been reported to have neuroprotective (43)(44)(45), antidepressant (46), antinociceptive (47), and anticonvulsant (28-33) effects, as well as cognition-enhancing effects (3)(4)(5)(6). The present study focused on the effects of NEF in amygdala-kindled seizures, one of the excellent experimental models for human complex partial seizures with secondary generalization (34,35), and compared the pyrrolidone-type AED, LEV.…”