Robustoxin, a
polypeptide consisting of a chain of 42
amino acid residues in a known sequence, has been isolated by
cation exchange chromatography from the crude
venom of the male funnel-web spider (Atrax robustus). Physiological activity or toxicity in the
venom fractions was detected by production of
fasciculation in mouse phrenic nerve-hemidiaphragm preparations and by lethality in new-born mice. In the present experiments in Macaca fascicularis monkeys anaesthetized with
pentobarbitone,
robustoxin (5-30 micrograms/kg infused i.v. over 5 min) produced immediate disturbances in respiration (including dyspnoea and apnoea), blood pressure and heart rate followed by severe
hypotension (mean systemic blood pressure less than 50 mmHg) or death due to respiratory and
circulatory failure within 196 min.
Robustoxin also produced lachrymation, salivation, generalized
skeletal muscle fasciculation and a parallel increase in body temperature, and increased firing in skeletal motor and autonomic nerves. These effects closely resembled those produced by i.v. infusions over 5 min of 50 micrograms/kg of crude
venom from male A. robustus spiders. Crude
venom from female A. robustus spiders (500 micrograms/kg i.v. over 5 min) produced some of the effects elicited by
robustoxin and crude
venom from male spiders, but to a much less marked extent. It was concluded that
robustoxin is responsible for the neurotoxic and lethal effects of human envenomation by male A. robustus spiders.