THE ANALGESIC ACTIVITY OF CROTAMINE, A NEUROTOXIN FROM CROTALUS DURISSUS TERRIFICUS (SOUTH AMERICAN RATTLESNAKE) VENOM: A BIOCHEMICAL AND PHARMACOLOGICAL STUDY ADRIANA C. MANCIN, 1 ANDREIMAR M. SOARES, 1 SILVIA H. ANDRIA Ä O-ESCARSO, 1 VITOR M. FAC ° A, 2 LEWIS J. GREENE, 2 SE  RGIO ZUCCOLOTTO, 3 IRENE R. PELA  4 and JOSE  R. GIGLIO 1 * 1 Departamento de BioquõÂmica, Faculdade de Medicina, Universidade de SaÄo Paulo, 14049 900 Ribeirao Preto S.P., Brazil, 2 Centro Interdepartamental de QuõÂmica de ProteõÂnas, Universidade de SaÄo Paulo, 14049 900 Ribeirao Preto S.P., Brazil, 3 Departamento de Patologia, Faculdade de Medicina, Universidade de SaÄo Paulo, 14049 900 RibeiraÄo Preto S.P., Brazil; and 4 Departamento de Farmacologia, Faculdade de CieÃncias FarmaceÃuticas, Universidade de SaÄo Paulo, 14049 900 RibeiraÄo Preto S.P., Brazil (Received 13 January 1998; accepted 9 April 1998) Adriana C. Mancin, Andreimar M. Soares, Silvia H. AndriaÄ o-Escarso, Vitor M. Fac ° a, Lewis J. Greene, SeÂrgio Zuccolotto, Irene R. Pela and Jose R. Giglio. The analgesic activity of crotamine, a neurotoxin from Crotalus duris- sus terri®cus (South American rattlesnake) venom: A biochemical and phar- macological study. Toxicon 36, 1927±1937, 1998.ÐCrotamine, a 4.88 kDa neurotoxic protein, has been puri®ed to apparent homogeneity from Crotalus durissus terri®cus venom by gel ®ltration on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss mice (20±25 g), it induced a time-dose depen- dent analgesic eect which was inhibited by naloxone, thus suggesting an opioid action mechanism. When compared with morphine (4 mg/kg), crota- mine, even in extremely low doses (133.4 mg/kg, i.p., about 0.4% of a LD 50 ) is approximately 30-fold more potent than morphine (w/w) as an analgesic. On a molar basis it is more than 500-fold more potent than morphine. It is also much more potent than the lower molecular weight crude fractions of the same venom. The antinociceptive eects 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 involved. His- topathological analysis of the brain, liver, skeletal muscles, stomach, lungs, spleen, heart, kidneys and small intestine of the crotamine injected mice did not show any visible lesion in any of these organs by light microscopy. Since crotamine accounted for 22% (w/w) of the desiccated venom, it was ident- i®ed as its major antinociceptive low molecular weight peptide component. # 1998 Elsevier Science Ltd. All rights reserved Toxicon Vol. 36, No. 12, pp. 1927±1937, 1998 # 1998 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0041-0101/98 $19.00 + 0.00 PII: S0041-0101(98)00117-2 * Author to whom correspondence should be addressed. 1927