Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission (PubMed:12911331). The toxin principally slows the inactivation process of TTX-sensitive sodium channels (PubMed:23685008). It discriminates neuronal versus muscular sodium channel, as it is more potent on rat brain Nav1.2/SCN2A (EC(50)=29 nM) than on rat skeletal muscle Nav1.4/SCN4A (EC(50)=416 nM) (PubMed:12911331). It also shows a weak activity on Nav1.7/SCN9A (EC(50)=1.76 uM) (PubMed:23685008). In vivo, the toxin produces pain hypersensibility to mechanical and thermal stimuli.(PubMed:23685008). It also exhibits potent analgesic activity (when injected intraperitoneally), increasing hot plate and tail flick withdrawal latencies in a dose-dependent fashion (PubMed:20619318). This paradoxical analgesic action, is significantly suppressed by opioid receptor antagonists, suggesting a pain-induced analgesia mechanism that involves an endogenous opioid system (PubMed:20619318). This led to hypothesis that pain relief induced by peripheral administration of Amm VIII may result from sensitization of primary afferent neurons and subsequent activation of an opioid-dependent noxious inhibitory control (PubMed:20619318). Expressed by the venom gland. Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta). LD(50) is 11.25 ug/kg by intracerebroventricular injection into mice but is not toxic (>1 mg/mouse) when injected subcutaneously. Does not act on Nav1.8/SCN10A and Nav1.9/SCN11A when tested on TTX-resistant sodium channels. Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.