A pharmacological examination of venom from the Papuan taipan (Oxyuranus scutellatus canni)

The Papuan taipan (Oxyuranus scutellatus canni) is the third most venomous terrestrial snake in the world, however, little is know about the pharmacol ogy of the venom. In the chick biventer cervicis muscle, venom (10 mu g/ml) abolished nerve-mediated twitches (time to 90% inhibition (t(90)) 44 +/- 5 min, n = 9). This inhibition was unaffected by prior incubation of the ven om with the phospholipase A inhibitor 4-bromophenacyl bromide (4-BPB; 0.72 mM) (t(90) 48 +/- 7 min, n = 8). The mouse phrenic nerve diaphragm preparat ion displayed greater sensitivity to venom (10 mu g/ml) (t(90) 75 +/- 1 min , n = 6). In the chick biventer muscle, venom (10 mu g/ml) significantly in hibited responses to acetylcholine (1 mM) and carbachol (20 mu M), but not KCl (40 mM), indicating activity at post-synaptic nicotinic receptors. Veno m (10 mu g/ml) did not affect direct muscle stimulation. Venom (3-30 mu g/m l) produced dose-dependant contractions of the guinea-pig ileum. Contractil e responses were significantly inhibited by indomethacin (1 mu M) or prior incubation of the venom with 4-BPB (0.72 mM) indicating involvement of a PL A component. In rat phenylephrine (0.3 mu M) precontracted aortae, venom (3 -100 mu g/ml) produced endothelium-independent relaxation which was unaffec ted by prior incubation of venom (30 mu g/ml) with 4-BPB (0.72 mM). In anae sthetised rats, 10 mu g/kg (i.v.) venom produced rapid respiratory and card iovascular collapse while 5 mu g/kg (i.v.) venom produced only a small tran sient decrease in mean arterial blood pressure. Prior administration of 5 m u g/kg (i.v.) venom enabled subsequent administration of 10 and 100 mu g/kg (i.v.) venom without respiratory or cardiovascular collapse. Further work is required to identify specific toxins with the above pharmacological acti vity. (C) 1999 Elsevier Science Ltd. All rights reserved.