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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cizolirtine citrate (E-4018) in the treatment of chronic neuropathic pain.

This study was performed to determine the efficacy and safety of oral cizolirtine citrate, a novel agent, in the treatment of chronic neuropathic pain. Cizolirtine was tested in a double-blind, placebo-controlled, two-way crossover study, having previously been shown to have significant analgesic and anti-hyperalgesic action in neuropathic pain models and preliminary human studies. Twenty-five patients with neuropathic pain, which was persistent for at least three months, and scored > 30 mm on a 100 mm visual analogue scale (VAS), were included. A subgroup of five patients had primary skin allodynia, i.e. pain evoked by non-noxious stimuli in the territory of the injured nerve. Cizolirtine 200 mg or placebo was administered twice daily for a treatment period of 21 days, each separated by a washout interval of 7 days. Assessments of skin allodynia were performed using the graded monofilaments (von Frey hairs) on days 1 (predose), 14 and 21 (90 min postdose). All patients were instructed to maintain a daily pain diary throughout the study. Results showed that the differences in VAS and allodynia scores between cizolirtine and placebo treatments were not significant in the overall analysis (p > or = 0.05); cizolirtine was well tolerated. In a subgroup of five patients with primary allodynia, a 53% reduction in VAS score from baseline at rest (p = 0.007) and 55% on movement (p = 0.0002) at day 21 was observed with cizolirtine, as compared to 8% at rest (p = 0.5215) and 13% on movement (p = 0.4187) with placebo. Similarly, allodynia improved with cizolirtine (p = 0.03) but not with placebo (p = 0.9) in this subgroup. Cizolirtine may be effective in primary allodynia after peripheral nerve injury, and a further trial in a larger number of such subjects is warranted.[1]


  1. Cizolirtine citrate (E-4018) in the treatment of chronic neuropathic pain. Shembalkar, P., Täubel, J., Abadias, M., Arezina, R., Hammond, K., Anand, P. Current medical research and opinion. (2001) [Pubmed]
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