Analgesic activity of piracetam: Effect on cytokine production and oxidative stress

Abstract

Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic.

The Combination of Antidepressant Duloxetine with Piracetam in Mice does not Produce Enhancement of Nootropic Activity

“…In addition to 5-HT and NE reuptake inhibitors, nootropic agents like piracetam [16] also play an important role in cognition. The dose range of piracetam described in package inserts of Nootrpil® is 2.4~12 gm per day [17]. The resulting dose range would be 34 to 171 mg/kg for an adult of 70 kg.…”

“…The resulting dose range would be 34 to 171 mg/kg for an adult of 70 kg. Navarro et al [17] showed therapeutic activity of piracetam at 100 mg/kg dose. Therefore, piracetam monotherapy was considered at 100 mg/kg dose in present study.…”

Effect of piracetam and nimodipine on full‐thickness skin burns in rabbits

“…The increase in lipid peroxidation is accompanied by T‐cell inhibition, with the latter inducing the normalisation of immunity by decreasing lipid peroxidation . Piracetam also has analgesic effects , reducing thermal hyperalgesia induced by tumour necrosis factor‐α (TNF‐α) . This property of the drug could be helpful in decreasing painful stimuli in skin burns.…”

“…Piracetam also favours the normalisation of immunity by effecting lipid peroxidation . In addition, it reduces peripheral inflammation and decreases neuropathic pain and thermal hyperalgesia .…”

Naringenin ameliorates pathological changes in liver and kidney of diabetic mice: a preliminary study / Naringenin reducira histopatološke promjene u jetri i bubregu miševa s dijabetesom

“…The levels of lipid peroxides were expressed as nmoles of malondialdehyde (MDA) formed per mg -1 protein. Protein concentration was determined as described by Navarro et al (16). Crystalline bovine serum albumin was used for calibration curve.…”