Paradoxin (PDX), purified from the Australian Elapid snake Oxyuranus microlepidotus venom is a little-studied toxin that belongs to the β-neurotoxin family, a group of potent snake neurotoxins having PLA 2 catalytic properties. PDX was first described 15 years ago as a taipoxin-like toxin (taipoxin is a three chain β-neurotoxin isolated from the Taipan snake, O. s. scutellatus). Since 1979, very few studies have been done on PDX and that led us to investigate its neurotoxic effects after central administration, with a particular focus on its potential convulsive activity as some β-neurotoxins have been observed to induce convulsions, and sometimes seizures. After intracerebroventricular (icv, lateral ventricle) injection of different doses through a stereotaxically implanted cannula, a four-step neurotoxic syndrome developed in rats. In most of the rats treated we did not notice seizures (ECoG recording) nor convulsions (visual observation). The mean lethal dose by icv route was inferred to bec. 1.2 μg/kg for these animals. A very similar kind of neurotoxic effect was observed in mice, stunned with ether and then injected directly through the skin near or in their third ventricle. LD 5 0 for mice was calculated to be 1.17 ± 0.08 μg/kg (n = 60), that is very close to that reported after iv injection (2 μg/kg). Gross histological examination (H and E staining) of the brain of the rats intoxicated by PDX did not show major target areas. Biochemical brain damage assessment is currently under investigation. In vitro experiments using rat hippocampal and striatal mini-slices were then carried out to determine the major neurochemical disturbances induced by PDX. In a preliminary superfusion experiment, PDX (100-200 nM) showed a slight tendency to increase ACh and Glu efflux from hippocampal mini-slices preincubated with [ 3 H]choline and [ 1 4 C]Glu. This effect did not seem to be related to a major leakage and is presently under investigation using a chemiluminescent technique. On the other hand PDX significantly increased the K + -evoked efflux of [ 3 H]DA from rat striatal mini-slices after 6 or 16 min of contact with the toxin during the superfusion. Testing the hypothesis that PDX could impair the uptake of the same neurotransmitters, we found that PDX actually did so, in an apparently calcium-independent way. Comparison with taipoxin is presented. Using a colorimetric assay PDX proved to be a weak enzyme as it is reported for taipoxin. In conclusion, PDX shares some of its pharmacological effects with other β-neurotoxins but the in vitro results are not sufficient to explain the complex neurotoxic syndrome observed that might involve several types of neurotransmission.