The toxicity of nigriventrine to rats was not evaluated due to the limited amount of material. However, animal behaviour under the effects of the nigriventrine was observed after ICV and peripheral application of the compound. The rats showed light convulsions 10 min after ICV

application (10 ng kg−1) of nigriventrine and were characterised by tonic–clonic crises that lasted up to 5 min. The Daporinad mw animals’ fur looked bristled, with partially diffuse piloerection localised around the neck and on the head. During the subsequent 15 min, the eyelids appeared partially closed with porphyrin accumulation around the eyes. The observed effects were transient, and the rats recovered fully after 30 min. In order to evaluate whether nigriventrine crosses the blood–brain barrier, it was peripherally administered to the animals (100 ng kg−1). The same clinical signs as reported above were observed by peripherical administration of nigriventrine, although they appeared in a milder form. These results suggested that nigriventrine might cross the blood–brain see more barrier. This type of incident was relatively common with P. nigriventer bites and could explain some of the convulsive effects reported after this type of accident. The compound hydroxyl-hydrazyl-dioxopiperidine [1,1′-(1-hydroxyhydrazine-1,2-diyl)bis(oxy)bis(4-hydroxy-2,6-dioxopiperidine-4

carboxylic acid)], generically named nigriventrine, was isolated and structurally characterised from the hydrophilic fraction of the venom from the “armed” spider P. nigriventer. It is a novel natural compound not previously reported amongst the venoms of venomous Arthropods. The dioxopiperidine moiety is uncommon amongst the LMM compounds from animal venoms. It has already been reported Anacetrapib as a basic building block of analgesic, anti-anxiety and anti-psychotic synthetic drugs (Gittos, 1989). This was the first report of a natural compound of animal origin presenting this type of chemical structure. The neuroactivity

of nigriventrine in rat brain was investigated through the monitoring of the pattern of expression of c-Fos protein, which is an inducible transcription factor whose activation is an important tool and a well-established marker to identify activated neurons in the autonomous or central nervous system after physical, chemical and/or biological stimuli (Kobelt et al., 2004). This assay revealed that nigriventrine acted in seven different brain regions: the motor cortex, sensory cortex, piriform cortex, median preoptic nucleus, dorsal endopiriform nucleus, lateral septal nucleus and hippocampus. In summary, nigriventrine may be considered a novel class of LMM spider venom toxin, belonging the group of hydroxyl-hydrazyl-dioxopiperidine compounds, which seems to be neuroactive at different rat brain regions. This the first LMM toxin reported in the venom of the “armed” spider P.