title: An effective anticonvulsant prepared following a host-guest strategy that uses hydroxypropyl-beta-cyclodextrin and benzaldehyde semicarbazone.
abstract: The convulsions of approximately 25% of epileptics are inadequately controlled by currently available medication; therefore the preparation of new antiepileptic drugs is of great interest. Aryl semicarbazones can be considered a new class of compounds presenting anticonvulsant activity. In addition, they can be orally administered and are more active as anticonvulsants than mephenytoin or phenobarbital. However, one disadvantage of these compounds is their low water solubility. As a strategy to circumvent this problem, a 1:1 inclusion compound of benzaldehyde semicarbazone (BS) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared and characterized. The anticonvulsant activities of the free semicarbazone and of the inclusion compound were evaluated in rats using the maximum electroshock and audiogenic seizures screenings. In both tests the minimum dose of compound necessary to produce activity decreases from 100mg/kg for the free semicarbazone to 35 mg/kg for the inclusion compound, indicating a significant increase in the bio-availability of the drug.
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, MG, Belo Horizonte, Brazil. beraldo@dedalus.lcc.ufmg.br
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Letícia R
authors.initials: LR
authors.lastname: Teixeira
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Vieira
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Doretto
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001547:Benzaldehydes / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures; D012664:Semicarbazones / Q000737:chemistry* / Q000627:therapeutic use; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
chemical_list: D000927:Anticonvulsants; D001547:Benzaldehydes; D003505:Cyclodextrins; D012664:Semicarbazones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin