title: Neuropharmacological profile of FrPbAII, purified from the venom of the social spider Parawixia bistriata (Araneae, Araneidae), in Wistar rats.
abstract: The aims of the present study were to investigate the anticonvulsant activity and behavioral toxicity of FrPbAII using freely moving Wistar rats. Moreover, the effectiveness of this compound against chemical convulsants was compared to that of the inhibitor of the GABAergic uptake, nipecotic acid. Our results show that FrPbAII was effective against seizures induced by the i.c.v. injection of pilocarpine (ED(50) = 0.05 microg/animal), picrotoxin (ED(50) = 0.02 microg/animal), kainic acid (ED(50) = 0.2 microg/animal) and the systemic administration of PTZ (ED(50) = 0.03 microg/animal). The anticonvulsant effect of FrPbAII differed from that of nipecotic acid in potency, as the doses needed to block the seizures were more than 10 folds lower. Toxicity assays revealed that in the rotarod, the toxic dose of the FrPbAII is 1.33 microg/animal, and the therapeutic indexes were calculated for each convulsant. Furthermore, the spontaneous locomotor activity of treated animals was not altered when compared to control animals but differed from the animals treated with nipecotic acid. Still, FrPbAII did not induce changes in any of the behavioral parameters analyzed. Finally, when tested for cognitive impairments in the Morris water maze, the i.c.v. injection of FrPbAII did not alter escape latencies of treated animals. These findings indicate that the novel GABA uptake inhibitor is a potent anticonvulsant with mild side-effects when administered to Wistar rats.
authors.affiliation: Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Erica Aparecida
authors.initials: EA
authors.lastname: Gelfuso
authors.forename: Alexandra Olimpio Siqueira
authors.initials: AO
authors.lastname: Cunha
authors.forename: Marcia Renata
authors.initials: MR
authors.lastname: Mortari
authors.forename: Jose Luiz
authors.initials: JL
authors.lastname: Liberato
authors.forename: Karina Haddad
authors.initials: KH
authors.lastname: Paraventi
authors.forename: Rene Oliveira
authors.initials: RO
authors.lastname: Beleboni
authors.forename: Joaquim
authors.initials: J
authors.lastname: Coutinho-Netto
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
authors.forename: Wagner Ferreira
authors.initials: WF
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C511624:2-amino-5-ureidopentanamide; D000927:Anticonvulsants; D018079:Receptors, GABA; D013111:Spider Venoms; D014508:Urea