title: Search for anticonvulsant and analgesic active derivatives of dihydrofuran-2(3H)-one.
abstract: A series of derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone, GBL) was synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In the anticonvulsant screening 10 lactones were effective in the maximal electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip, mice). Statistical analysis showed correlation between the anticonvulsant activity and relative lipophilicity parameters determined by experimental and computational methods (R(M0), ClogP and MlogP). Preliminary antinociceptive evaluation of selected derivatives revealed strong analgesic activity. The majority of the tested compounds showed high efficacy in animal models of acute pain (hot plate and writhing tests) and strong local anesthetic activity (modified tail immersion test). The obtained ED(50) values were comparable with such analgesics as acetylsalicylic acid and morphine.
authors.affiliation: Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Więckowski
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.forename: Justyna
authors.initials: J
authors.lastname: Bytnar
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
mesh_terms: D015107:4-Butyrolactone / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D051379:Mice; D010146:Pain; D010147:Pain Measurement / Q000187:drug effects*
chemical_list: D000700:Analgesics; D000779:Anesthetics, Local; D000927:Anticonvulsants; D015107:4-Butyrolactone