Anticonvulsant and anxiolytic activity of FrPbAII, a novel GABA uptake inhibitor isolated from the venom of the social spider Parawixia bistriata (Araneidae: Araneae).
This study was aimed at determining the effects of FrPbAII (174 Da), a novel isolated component from Parawixia bistriata spider venom, in the CNS of Wistar rats. Considering that FrPbAII inhibits the high affinity GABAergic uptake in a dose-dependent manner, its anxiolytic and anticonvulsant effects were analyzed in well-established animal models. Injection of FrPbAII in the rat hippocampus induced a marked anxiolytic effect, increasing the occupancy in the open arms of the elevated plus maze (EC(50)=0.09 microg/microl) and increasing the time spent in the lit area of the light-dark apparatus (EC(50)=0.03 microg/microl). Anxiolytic effects were also observed considering the number of entries in the open arms of the EPM and in the lit compartment of the light-dark box. Interestingly, when microinjected bilaterally in the SNPr of freely moving rats, FrPbAII (0.6 microg/microl) effectively prevented seizures induced by the unilateral GABAergic blockade of Area tempestas (bicuculline, 0.75 microg/microl). This anticonvulsant effect was similar to that evoked by muscimol (0.1 microg/microl) and baclofen (0.6 microg/microl), but differed from that of the specific GAT1 inhibitor, nipecotic acid (0.7 microg/microl). This difference could be accounted either for the parallel action of FrPbAII over glycinergic transporters or to an inspecific activity on GABAergic transporters. Data from the present investigation might be pointing to a novel compound with interesting and yet unexplored pharmacological potential.
Liberato
José Luiz
JL
Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature, University of São Paulo, Brazil.
Cunha
Alexandra Olimpio Siqueira
AO
Mortari
Márcia Renata
MR
Gelfuso
Erica Aparecia
EA
Beleboni
René de Oliveira
Rde O
Coutinho-Netto
Joaquim
J
dos Santos
Wagner Ferreira
WF
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline; D002755:Choice Behavior / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009557:Nipecotic Acids; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013111:Spider Venoms / Q000737:chemistry* / Q000494:pharmacology; D013112:Spiders / Q000737:chemistry; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C511624:2-amino-5-ureidopentanamide; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D009557:Nipecotic Acids; D013111:Spider Venoms; C030278:nipecotic acid; D014508:Urea; D003975:Diazepam; D010433:Pentylenetetrazole; D001640:Bicuculline