Phlotoxin 1

Its venom, which includes several neurotoxic peptides like phlotoxin, targets diverse ion channels and chemical receptors.

[1] The structure of phlotoxin comprises six cysteine residues forming an ICK architecture fold, with amidation occurring at the C-terminus.

[1] In examining the effects of PhlTx1 on the sodium channel Nav1.7/β1, it appears to share similarities with TTX (tetrodotoxin).

Both PhlTx1 and TTX exhibit a capacity to block the channel pore, resulting in a noticeable decrease in sodium currents.

Its potential as an antinociceptive agent became apparent when a loss-of-function mutation in the NaV1.7 gene resulted in a congenital inability to perceive pain.

[5] The mechanism underlying the synergistic effect of opioid receptor agonists with selective NaV1.7 inhibitors remains unknown, but this discovery presents a novel approach to pain management.

[7] However, the poor selectivity towards the hNav1.5 and 1.6 subtypes may be associated with in vivo cardiac and neuromuscular side effects, respectively, which could limit its potential use as an analgesic molecule.