title: Development of ligands at γ-aminobutyrric acid type A (GABAA) receptor subtype as new agents for pain relief.
abstract: The identification of compounds with selective anxiolytic-like effects, exerted through the benzodiazepine site on γ-aminobutyric acid type A (GABA(A)) receptors, and that show pronounced antihyperalgesia in several pain models, has oriented research towards the development of new agents for the relief of pain. Starting from our previously reported ligands at the benzodiazepine site on GABA(A) receptors showing selective anxiolytic-like effects, we have designed new compounds with the aim of identifying those devoid of the typical side effects of the classical benzodiazepines. Our preliminary results indicate that compounds 4, 10(±) and 11 have a very promising antihyperalgesic profile in different animal pain models (peripheral mono-neuropathy, STZ-induced hyperalgesia). In particular 11 exhibits high potency since it exerted its protective effect starting from the dose of 3mg/kg po, after single injection.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente attivi (HeteroBioLab) Università degli Studi di Firenze, Via U. Schiff, 6, 50019 Polo Scientifico, Sesto Fiorentino, Italy. gabriella.guerrini@unifi.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guerrini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ciciani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bruni
authors.forename: Silvia
authors.initials: S
authors.lastname: Selleri
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Simona
authors.initials: S
authors.lastname: Daniele
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Annarella
authors.initials: A
authors.lastname: Costanzo
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010433:Pentylenetetrazole; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013311:Streptozocin; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D014227:Triazines; D013311:Streptozocin; D010433:Pentylenetetrazole