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Effects of the novel analgesic, cizolirtine, in a rat model of neuropathic pain

Kayser, Valériea,∗; Farré, Antoniob; Hamon, Michela; Bourgoin, Sylviea

doi: 10.1016/S0304-3959(02)00497-9
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Cizolirtine (5-{[(N,N-dimethylaminoethoxy)phenyl]methyl}-1-methyl-1H-pyrazol citrate) is a centrally acting analgesic with a currently unknown mechanism of action, whose efficacy has been demonstrated in various models of acute and inflammatory pain in rodents. Further studies were performed in order to assess its potential antinociceptive action in a well-validated model of neuropathic pain, i.e. that produced by unilateral sciatic nerve constriction in rats. Animals were subjected to relevant behavioural tests based on mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to paw immersion in a cold (10°C) water bath) stimuli, 2 weeks after sciatic nerve constriction, when pain-related behaviour was fully developed. Acute pretreatment with 2.5–10 mg/kg p.o. of cizolirtine reversed both mechanical and thermal allodynia. These effects were antagonized by prior injection of the α2-adrenoceptor antagonist idazoxan (0.5 mg/kg i.v.), but not the opioid receptor antagonist naloxone (0.1 mg/kg i.v.). On the other hand, cizolirtine (10 mg/kg p.o.) produced no motor deficits in animals using the rotarod test.

Our study showed that cizolirtine suppressed pain-related behavioural responses to mechanical and cold stimuli in neuropathic rats, probably via an α2-adrenoceptor-dependent mechanism. These results suggest that cizolirtine may be useful for alleviating some neuropathic somatosensory disorders, in particular cold allodynia, with a reduced risk of undesirable side effects.

aINSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 91, Boulevard de l'Hôpital, 75634 Paris Cedex 13, France

bLaboratorios Dr Esteve, S.A., Avenue Mare de Déu de Montserrat, 221, 08041 Barcelona, Spain

Corresponding author. Tel.: +33–1–4077–9709; fax: +33–1–4077–9790

E-mail: kayser@ext.jussieu.fr

Submitted September 5, 2002; accepted December 18, 2002.

© 2003 Lippincott Williams & Wilkins, Inc.
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