SEPARATION OF BUNGARUS FASCIATUS VENOM AND PRELIMINARY PHARMACOLOGICAL STUDIES OF ITS TOXIC COMPONENTS

The venom of Bungarus fasciatus was separated into seventeen fractions in a CM-cellulose column with ammonium acetate buffer by linear pH and ionic strength gradient elution. Fractions Ⅺ, Ⅻ and ⅩⅤ were shown to be cardiotoxic principles similar :to cobra card iotoxinand fraction ⅩⅢ and ⅩⅣ were neurotoxic principles which acted on the p ostsynaptics N-cholinergic receptors of the motor endplate.The cardiotoxic fractions were shown to produce systolic standstill ofthe isolated rat heart, to induce contracture of the baby chick biventer cervicis muscle and to produce local irritation on rabbit eyes. Fraction ⅩⅤ exhibited direct hemolytic activity on washed guinea pig erythrocytes.Fraction ⅩⅢ was shown, to be a neurotoxin on neuromuscular preparations. The twitch response of the skeletal muscle to indirect stimulation were progressively abolished in the baby chick biventer ceryicis muscle, the rat phrenic nerve diaphragm and the frog sartorium, muscle, while the responses to direct stimulation or to high K⁺ were not appreciably affected. The Ach release of the rat phrenic nerve ending was also unaffected. The response to Ach (even 10 times the initial) was completely abolished inthe chick biventer cervicis muscle. The Ach dose-response curve was shifted to the right and was antagonized by neostigmine. The blocking actions were partially reversible in frog sartorium muscle and rat phrenic nerve diaphragm after repeated washings with physiological solution. It is concluded that fraction ⅩⅢ is a neurotoxin which acts on postsynaptic cholinergic receptors of motor endplate to produce nondepolarization type neuromuscular block.