Antiallodynic effect and side effects of Phα1ß, a neurotoxin from the spider Phoneutria nigriventer: comparison with ω-conotoxin MVIIA and morphine.

Phα1ß is a potent toxin obtained from the spider Phoneutria nigriventer that blocks neuronal voltage-sensitive Ca(2+) channels. This study compared the antiallodynic effects of Phα1ß, ω-conotoxin MVIIA and morphine in mice and their side effects in rats. Mechanical allodynia was measured in mice receiving single intrathecal administration of Phα1ß, ω-conotoxin MVIIA or morphine before or after the incisional plantar procedure. The effect of the treatments on cardiovascular profile and global neurological were evaluated in rats. The expression of pro or anti-inflammatory cytokines of human polymorph mononuclear cells was also evaluated. Preemptive use of ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site) induced shorter antiallodynic effect than Phα1ß (100 pmol/site) in mice. Post-incision administration of Phα1ß (200 pmol/site) induced longer mechanical antiallodynic effect than ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site). Intrathecal injection of Phα1ß (200 pmol/site) and morphine (433 pmol/site) did not change while ω-conotoxin MVIIA (100 pmol/site) increased the heart rate in rats 3 h after its administration. Phα1ß (200 pmol/site), ω-conotoxin MVIIA (100 pmol/site) and morphine (433 pmol/site) did not change mean arterial pressure 0.5 and 3 h after their administration. The treatments did not alter neurological performance assessed by global neurological evaluation and open-field test. The tested drugs did not induced expression of pro or anti-inflammatory cytokines in CD4 monocytes. In conclusion, preemptive administration Phα1ß in mice induced longer antiallodynic effect than ω-conotoxin MVIIA and morphine. Phα1ß also induced a longer mechanical antiallodynic effect than ω-conotoxin MVIIA and morphine when used after the surgical incision. The present results suggest that Phα1ß has a potential application in the management of postoperative pain with low side effects.

Effects of new Phoneutria spider toxins on glutamate release and [Ca2+]i in rat cortical synaptosomes.

Studies revealed that the venom of the Brazilian "armed" spider Phoneutria nigriventer contains potent neurotoxins that caused excitatory symptoms such as salivation, lachrymation, priapism, convulsions, flaccid and spastic paralysis. It was also reported that the main mechanism of action of those neurotoxins are effects on ion channels such as inhibition of the inactivation of Na+ channels, blockage of K+ channels and blockage of calcium channels. The venom from Phoneutria keyserlingi, as might be expected, contains a series of polypeptides that are very similar, but not identical, to the proteins previously obtained from the venom of P. nigriventer in terms of their amino acid sequences and biological activities. We evaluated the effects of some of the toxins of P. nigriventer and P. keyserlingi on glutamate release and the decrease in [Ca2+]i by using synaptosomes of rat brain cortices and fluorimetric assays. Sequence comparisons between the Phoneutria toxins of both the species showed great similarity in the location of cysteine residues. However, thus far, no pharmacological assays were performed to evaluate the extension of those biochemical modifications. Our results showed that differences between the amino acid sequences of Phoneutria toxins of both the species lead to the significant changes in the pharmacological properties of these toxins.