Phα1β is a
neurotoxin purified from
spider venom that acts as a high-voltage-activated (HVA)
calcium channel blocker. This spider
peptide has shown a high selectivity for N-type HVA
calcium channels (NVACC) and an
analgesic effect in several animal models of
pain. Its activity was associated with a reduction in
calcium transients,
glutamate release, and
reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat
chronic pain reverted
opioid tolerance with a safer profile than ω-
conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified.
CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the
intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant
pain models and its mechanisms of action, highlighting the impact of
CTK 01512-2 synthesis and its potential for multimodal
analgesia.