The activation of diazinon by ganglia of the cockroach Periplaneta americana L. and its action on nerve conduction and cholinesterase activity

When sixth abdominal ganglia of the cockroach Periplaneta americana were irrigated continuously with diazinon solution in situ, its effects on nerve conduction and cholinesterase activity closely resembled those of diazoxon; spontaneous activity and after-discharge increased until conduction was blocked, which happened while some cholinesterase was still uninhibited. The symptoms were only slightly relieved by irrigating ganglia with saline. Though the LD50's of diazinon and diazoxon applied topically to adult male P. americana were similar (2.5 ± 0.33 and 4.5 ± 0.38 μig. per insect), diazoxon was about 300 times more active than diazinon against nerve function and cholinesterase activity in the sixth abdominal ganglion. This is probably because in the nerve preparations contact between the insecticide and the tissues surrounding the nerve cord, which in whole insects convert diazinon, a thionophosphate, into its phosphate analogue diazoxon, a more active anticholinesterase, was minimized. Indeed, taking into account the evidence of workers who previously compared in vitro the anticholinesterase activities of several thionophosphates with those of their phosphate analogues and found the phosphates much more active, the effect of diazinon on cholinesterase activity and nerve function in our experiments was unexpectedly great. By applying diazinon to nerve cords with SKF 525-A, a compound likely to prevent oxidation of diazinon to diazoxon, an attempt was therefore made to decide whether diazinon directly affected nerve conduction or whether the effect resulted either from its conversion to diazoxon within the nerve tissue or from impurities in the diazinon used. Results were inconclusive, for SKF 525-A (p-diethylaminoethyl diphenylpropylacetate hydrochloride) not only failed to prevent the inhibition of cholinesterase, but interfered with the action of both diazinon and diazoxon on nerve conduction, and itself affected nerve conduction when applied alone. The possibility that diazinon is itself a mild anticholinesterase was not excluded. SKF 525-A applied to sixth abdominal ganglia at 2 × 10^-4M blocked conduction from cereal nerves to giant fibres in 50–97 min. and at 4 × 10^-5M decreased the post-synaptic response; applied to giant fibres at 2 × 10^-4M it blocked conduction in 90–208 min. The effects of the larger concentration were not completely reversible. Although SKF 525-A has been widely used to study the metabolism of drugs, its direct effects on conduction in nerve axons seem not to have been noted previously.