THE ANALGESIC ACTIVITY OF CROTAMINE, A NEUROTOXIN FROM CROTALUS-DURISSUS-TERRIFICUS (SOUTH-AMERICAN RATTLESNAKE) VENOM - A BIOCHEMICAL AND PHARMACOLOGICAL STUDY

Crotamine, a 4.88 kDa neurotoxic protein, has been purified to apparen t homogeneity from Crotalus durissus terrificus venom by gel filtratio n on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss m ice (20-25 g), it induced a time-dose dependent analgesic effect which was inhibited by naloxone, thus suggesting an opioid action mechanism . When compared with morphine (4 mg/kg), crotamine, even in extremely low doses (133.4 mu g/kg, i.p., about 0.4% of a LD50) is approximately 30-fold more potent than morphine (w/w) as an analgesic. On a molar b asis it is more than 500-fold more potent than morphine. It is also mu ch more potent than the lower molecular weight crude fractions of the same venom. The antinociceptive effects of crotamine and morphine were assayed by the hot plate test and by the acetic acid-induced writhing method. Therefore, both central and peripheral mechanisms should be i nvolved. Histopathological analysis of the brain, liver, skeletal musc les, stomach, lungs, spleen, heart, kidneys and small intestine of the crotamine injected mice did not show ally visible lesion in ally of t hese organs by light microscopy. Since crotamine accounted for 22% (w/ w) of the desiccated venom, it was identified as its major antinocicep tive low molecular weight peptide component. (C) 1998 Elsevier Science Ltd. All rights reserved.