title: Synthesis and biological evaluation of novel dimiracetam derivatives useful for the treatment of neuropathic pain.
abstract: 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.
authors.affiliation: Brane Discovery, Insubrias Biopark, Via Lepetit 34, 21040 Gerenzano, Varese, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Farina
authors.forename: Stefania
authors.initials: S
authors.lastname: Gagliardi
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Marisa
authors.initials: M
authors.lastname: Martinelli
authors.forename: Monica
authors.initials: M
authors.lastname: Norcini
authors.forename: Carlo
authors.initials: C
authors.lastname: Parini
authors.forename: Paola
authors.initials: P
authors.lastname: Petrillo
authors.forename: Silvano
authors.initials: S
authors.lastname: Ronzoni
mesh_terms: 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
chemical_list: D007093:Imidazoles; D011758:Pyrroles; C085079:dimiracetam