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NiK-13317, a novel dimiracetam derivative for the treatment of neurophatic pain
Carlo Farina, Carla Ghelardini, Nicoletta Galeotti, Stefania Gagliardi, Giuseppe A.M. Giardina,
Marisa Martinelli, Carlo Parini, Paola Petrillo, Roberto Rigolio
34th Annual Meeting Neuroscience Society (Oct 23-27, San Diego), 2004, Abstract 863.7
It has been reported recently [1] that nefiracetam, a lipophilic analog of piracetam, was able to
reverse dose dependently the mechanical and thermal hyperalgesia induced by partial ligation
of the sciatic nerve in mice. This analgesic effect was not opioid mediated, as it was not
reversed by naloxone. Chemical modifications of the structure of dimiracetam, [2] a bicyclic
analog of the nootropic piracetam, afforded a small array of novel derivatives among which
NiK-13317 displayed a very promising antihyperalgesic profile. In the rat models of neuropathic
pain induced either by chronic constriction injury of sciatic nerve or by streptozotocin, NiK-
13317 (50 mg/kg p.o.) completely reverted the reduction of pain threshold evaluated by the
paw-pressure test. NiK-13317 exerted its antihyperalgesic effect at a supraspinal level since it
was effective also after i.c.v. administration (3-30 µg i.c.v.). The activity of NiK-13317 was also
confirmed in a mouse model of neuropathy induced by injection of streptozotocin, in which a
thermal painful stimulus was applied to evaluate the pain threshold (hot-plate). NiK-13317
showed an antihyperalgesic effect of intensity comparable to that exerted by the well-known
antineuropathic drug gabapentin (100 µg i.c.v.), and it was more effective than ethosuximide
(500 µg i.c.v.) or levetiracetam (500 µg i.c.v.). NiK-13317 was devoid of any effects when
administered in the absence of pre-existing painful conditions. Furthermore, in the range of
antihyperalgesic doses, it did not produce any behavioral impairment as evaluated by the
rotarod test. These results suggest that NiK-13317 might represent a novel and well tolerated
therapeutic agent for the relief of neuropathic pain.
[1] Rashid H., Ueda H. J. Pharm. Exp. Ther. 2002, 303, 226.
[2] Pinza M, et al. J Med Chem. 1993, 36, 4214.