The analgesic activity of crotamine, a neurotoxin from Crotalus durissus terrificus (South American rattlesnake) venom: A biochemical and pharmacological study

• Published in: Toxicon (Oxford) Vol. 36; no. 12; pp. 1927 - 1937
• Main Authors: Mancin, Adriana C., Soares, Andreimar M., Andrião-Escarso, Silvia H., Faça, Vitor M., Greene, Lewis J., Zuccolotto, Sérgio, Pelá, Irene R., Giglio, José R.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01-12-1998; Elsevier Science
• Subjects: Analgesics - pharmacology; Animals; Biological and medical sciences; Chromatography, Gel; Chromatography, High Pressure Liquid; Crotalid Venoms - pharmacology; Crotalus - physiology; Crotalus durissus terrificus; General pharmacology; Male; Medical sciences; Mice; Naloxone - pharmacology; Naloxone - toxicity; Neurotoxins - pharmacology; Pain Measurement; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Intraperitoneal administration; Purification; Rodentia; Animal origin; Biological activity; Ophidia; Toxin; Vertebrata; Mammalia; Analgesic; Mouse; Animal; Venom; Subcutaneous administration; Reptilia
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(98)00117-2

Crotamine, a 4.88
kDa neurotoxic protein, has been purified to apparent homogeneity from
Crotalus durissus terrificus venom by gel filtration on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss mice (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
μg/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 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 involved. Histopathological 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 identified as its major antinociceptive low molecular weight peptide component.