Mode of action of β-carboline convulsants on the insect nervous system and their potential as insecticides

Abstract

Little information is available on the actions of β-carboline convulsants on insect GABA receptors or their potential as insecticides. Accordingly, two compounds (3-ethoxy-β-carboline, 3-EBC; dimethoxy-β-carboline-3-methyl ester, DMCM) were studied for their effects on Drosophila melanogaster larval neuron discharge and also in lethality bioassays on adult female D. melanogaster and adult male Blattella germanica. Recordings of nerve spiking in the isolated larval central nervous system showed that 3-EBC and DMCM inhibited nerve discharge, and this inhibitory effect was not additive with that of GABA, confirming that the inhibition was expressed through an action on the GABA receptor. Nerve blockage induced by β-carbolines could not be reversed by picrotoxinin, indicating that there may exist some overlap or negative allosteric coupling between the picrotoxinin and β-carboline binding sites. DMCM and 3-EBC effectively antagonized the effects of exogenously applied GABA in nerve preparations from insecticide-susceptible larvae. In contrast, preparations from the rdl strain of D. melanogaster, which possesses a GABA receptor that is highly resistant to cyclodienes and related convulsants, were less sensitive to the GABA antagonist effect of DMCM. Neither of the β-carbolines produced any appreciable mortality in insects, even when synergized with piperonyl butoxide or S,S,S-tributyl phosphorotrithioate, The toxicity of the β-carbolines is probably limited by their relatively weak effects on the GABA receptor and perhaps also by pharmacokinetic factors. These considerations, coupled with the cross-resistance observed in cyclodiene-resistant insects, suggest that the currently available β-carbolines are not viable as lead compounds for insecticide screening efforts. © 1997 SCI.