Activity of neurotoxins isolated from the venom of Bufo paracnemis on PTZ-induced seziures and voltage-dependent Na+, K+ e Ca++ ion channels.

• Grant number: 07/06742-8
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2008
• Effective date (End): April 30, 2009
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Wagner Ferreira dos Santos
• Grantee: Alexandra Olimpio Siqueira Cunha
• Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 05/54855-0 - Animal toxins: structure, function and biotechnological applications, AP.TEM

Abstract

Through the evolutionary process, an arsenal of compounds have particularly favored venomous animals, which use these molecules as a unique way to paralyze and/kill their preys. The targets of many neurotoxins include ionic channels permeable to Na+, K+ and Ca++ ions, which control a wide range of physiological processes in several biological systems, but remarkably in the CNS. Channel malfunction is often associated to important neurological conditions, such as: epilepsies, cardiac arrhythmia and chronic pain. Therefore, ion channels have been subject of extensive studies and in most cases; their pharmacological characterization has been possible due to the specificity of animal neurotoxins. The most studied groups of venomous animals include venoms of scorpions, spiders, marine snails, frogs and snakes. Despite of the great pharmacological potential of neurotoxins, very few analogues of these compounds have been put into clinical practice until now. However, as new methodologies for isolation and analogue synthesis may emerge, it is possible that very soon a novel generation of neuroactive compounds of animal venom origin may be available for both basic research and clinical practice. Therefore, the aims of the present study are: 1. Characterize the activities of neurotoxins from the venom of the frog Bufo paracnemis on Na+, K+ and Ca+2 channels and 2. Analyze the anticonvulsant potential of these toxins against generalized seizures induced by the systemic administration of PTZ.