sFTX-3.3

Polyamine amide spider toxins inhibit neuronal voltage-activated Ca²⁺ currents. A terminal arginine group is an important feature of these Ca²⁺ channel antagonists^1-2.

FTX is a polyamine component of the venom of the American funnel web spider Agelenopsis aperta, and has been described as a selective antagonist of P-type voltage-dependent Ca²⁺ channels^3-4. However, it has been demonstrated that FTX has actions at other sites including NMDA and GABA receptors and also on T-type calcium channels⁵.

sFTX-3.3, a synthetic funnel web spider toxin^6-7, is a polyamine amide analogue of FTX. The structures of these polyamine containing compounds are not identical: sFTX-3.3 contains an amide carbonyl oxygen that is absent from the predicted structure of native FTX⁸. sFTX-3.3 has been shown to block P-type calcium channels in rat cerebellar Purkinje cells⁸ and antagonizes P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar potencies. Its IC₅₀ against P-, N-, and L-type channels are ~0.24 mM, ~0.7 mM and ~0.7 mM, respectively⁹.