Some pharmacological studies of venom from the inland taipan ( Oxyuranus microlepidotus)

The present study was designed to obtain a basic pharmacological profile of venom from the inland taipan ( Oxyuranus microlepidotus). Venom (0.05–50 μg/ml) produced dose-dependent contractions in guinea-pig ileum, which could not be reproduced upon second administration. The cyclooxygenase inhibitor indomethacin (1 μM), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A 2 (PLA 2) by incubation with 4-bromophenacyl bromide (1.8 mM) all significantly inhibited responses to venom (0.5 μg/ml). Venom (0.5 μg/ml) caused inhibition of stimulation-induced contractions in the prostatic segment of rat vas deferens which was not significantly affected by the α 2-adrenoceptor antagonist idazoxan (0.3 μM). Venom (10 μg/ml) caused time-dependent inhibition of the rat electrically stimulated phrenic nerve–diaphragm preparation, positive inotropic and chronotropic responses in rat isolated atria and relaxation in rat endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae, the nitric oxide synthase inhibitor N-nitro- l-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 μg/ml). Venom (50 μg/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 μg/kg, i.v.) caused a gradual fall in blood pressure which was sometimes accompanied by a temporary cessation of respiration. A PLA 2 assay detected the presence of PLA 2 in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachidonic acid metabolites and a component capable of relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve–diaphragm is probably due to the previously identified neurotoxin (paradoxin).