Inhibitor Report for: Salioxon

Chemical and biochemical studies on three types of cyclic phosphoryl compounds are discussed in connection with the development of insecticides. They are five-membered cyclic phosphoramidates (I), six-membered cyclic phosphates (II) and bridged bicyclic phosphates (III). Development of I has started from the finding of L-leucine as a neuroactive substance in silkworm blood, followed by its combination with chemically active five-membered cyclic phosphates. Studies on the metabolism of neurotoxic tri-o-tolyl phosphate caused the invention of the insecticide salithion in the series of II. Salithion was chemically converted into its thiolo isomers, which is a convenient phosphorylating agent useful to synthesize biologically interesting phosphate esters. III does not inhibit acetylcholin-esterase but acts as an anti-GABA agent.

Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B-receptor binding activity with 3H-norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B-receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in-vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.