Synthesis and biological evaluation of novel dimiracetam derivatives useful for the treatment of neuropathic pain.
Chemical modifications of dimiracetam, a bicyclic analogue of the nootropic drug piracetam, afforded a small set of novel derivatives that were investigated in in vivo models of neuropathic pain. Compounds 5, 7 and 8 displayed a very promising antihyperalgesic profile in rat models of neuropathic pain induced by both chronic constriction injury of the sciatic nerve and streptozotocin. The compounds completely reverted the reduction of pain threshold evaluated by the paw pressure test. Importantly these derivatives did not induce any behavioural impairment as evaluated by the rotarod test. These results suggest that compounds 5, 7 and 8 might represent novel and well-tolerated therapeutic agents for the relief of neuropathic pain.
Farina
Carlo
C
Brane Discovery, Insubrias Biopark, Via Lepetit 34, 21040 Gerenzano, Varese, Italy.
Gagliardi
Stefania
S
Ghelardini
Carla
C
Martinelli
Marisa
M
Norcini
Monica
M
Parini
Carlo
C
Petrillo
Paola
P
Ronzoni
Silvano
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
D007093:Imidazoles; D011758:Pyrroles; C085079:dimiracetam