Journal of Pharmacy and Pharmacology 2 (2014) 439-452 Phoneutria Spider Toxins Target Channels Involved in Cardiac Arrhythmias, Ischemia and Pain Marcus Vinicius Gomez 1 , Célio J. Castro-Junior 1 , Marta Nascimento Cordeiro 2 , Renato Santiago Gomez 3 and Juliano Ferreira 4 1. Department of Neurotransmitters, Institute of Education and Research, Santa Casa, Belo Horizonte, Minas Gerais 30150-240, Brazil 2. Department of Biochemistry, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais 30510-010, Brazil 3. Department of Surgery, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil 4. Department of Pharmacology, Biological Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina 80040-900, Brazil Abstract: Toxins isolated from the venom of the spider Phoneutria nigriventer either inhibit or activate a vast number of targets, such as ion channels, with high selectivity and affinity. PhTx3-1 toxin is a selective blocker of IA currents of K + channels, and PhTx3-3 and PhTx3-4 are calcium channel blockers of the P/Q-type calcium channels. The spider neurotoxin PhTx3-6 reversibly and non-specifically inhibits high-voltage-activated Ca 2+ channels with varying potency (N > R > P/Q > L) in heterologous and native systems. There has been a huge increase in the range of medical disorders involving ionic channels, and blockers of these channels have potential as therapeutic agents. The mechanism of action of each toxin family is different; thus, each needs to be evaluated for its therapeutic potential. This review will focus on peptide toxins purified from the venom of the spider Phoneutria nigriventer that are currently being evaluated in preclinical tests as possible drugs for the treatment of pain, cardiac arrhythmias and ischemia. Key words: Phoneutria nigriventer, toxins, pain, arrhythmias, ischemia, ion channels. 1. Introduction A large number of organisms produce and secrete venoms to defend themselves and capture prey. Poisonous animals have developed effective strategies to paralyze and/or kill prey, which makes them very successful hunters and fearless defenders against larger predators. Venom is a rich source of biochemically active enzymes, proteins, peptides and low-molecular-weight substances. Toxins isolated from spider venoms either inhibit or activate a vast number of targets, such as ion channels, with high selectivity and affinity [1]. For this selectivity, these animals received the help of several million years of evolution to generate and select toxins. Thus, nature Corresponding author: Marcus Vinicius Gomez, Ph.D., professor, research field: toxinology. E-mail: marcusvgomez@gmail.com. has evolved venoms into a huge pharmacological library of active pharmaceuticals with high selectivities and affinities, which can be explored as therapeutics or serve as templates for drug design. In general, the toxins can be roughly divided into non-peptide and peptide toxins. Peptide toxins are generally synthesized in the venomous ducts of poisonous creatures. The majority of the data acquired to date have been from toxins isolated from the venoms of snakes, scorpions, spiders, marine snails (Conus genus) and sea anemones. The present review focuses on the efforts of our group during the last 20 years to determine the pharmacologic actions and therapeutic potential of toxins from the venom of the aggressive Brazilian spider Phoneutria nigriventer. This spider is responsible for most human accidents in the southeast of Brazil, and thus, the study of its venom is of relevance to public health [2]. Moreover, there are D DAVID PUBLISHING