POTENTIAL ANALGESIC EFFECTS OF ANIMAL TOXINS: FROM BASIC RESEARCH TO CLINICAL APPLICATION

YARA CURY(1)

(1)Laboratory of Pathophysiology, Butantan Institute, São Paulo, Brazil

Pain is a major symptom of many different diseases. Identification of mechanisms and molecular components responsible for pain generation has contributed to the advance in pain control as well as to the selection of new targets for designing novel analgesic drugs. The potential use of natural products as analgesics is well documented. In this context, the selectivity / specificity of animal toxins have enabled their use as potential therapeutics in the treatment of pain, making them candidates for the development of new analgesic drugs. Experimental data have indicated that spider and scorpions peptide toxins induce analgesia by selectively inhibiting voltage-gated ion channels, ASIC channels, or glutamate receptors. Amphibian skin alkaloids that are potent agonists of nicotinic acetylcholine receptor and amphibian peptide opioids have been shown to produce analgesia in humans and animals. The marine environment has proven to be a very rich source of compounds endowed with potent antiinflammatory and analgesic activities. Prialt® (ziconotide intrathecal infusion, Elan Pharmaceuticals Inc.) is the first peptide derived from studies with Conus toxins, which was approved by the United States Food and Drug Administration for use in humans as analgesic. Snake venoms comprise a complex mixture of active substances, which can display toxic activities. Despite of their toxicity and based on their biological actions, snake venom components have been used as therapeutic agents as well as scientific tools for the comprehension of physiological and pathophysiological processes. Several lines of evidence indicate that various elapid and viperid venoms display central and peripheral analgesia, mediated by opioidergic or cholinergic mechanisms. The analgesic effect of these venoms has been credit to neurotoxins, small myotoxins, as well as to non-toxic venom constituents. Recently, crotalphine, a novel k- and d-opioid receptor agonist, was obtained from the venom of the snake Crotalus durissus terrificus. This peptide displays potent and long-lasting analgesic effect, being able to inhibit inflammatory, neuropathic and cancer pain. The pre-clinical trials with crotalphine are now in progress.

KEY WORDS: Animal toxins, analgesia, ion channels, opioid receptors, cholinergic receptors, NA transporter

CORRESPONDENCE TO : YARA CURY, Laboratory of Pathophysiology, Butantan Institute, Sao Paulo, Brazil, Phone: +55 11 37267222. Fax: +55 11 37261505. Email: yarac@attglobal.net