MODE OF ACTION OF BETA-CARBOLINE CONVULSANTS ON THE INSECT NERVOUS-SYSTEM AND THEIR POTENTIAL AS INSECTICIDES

Little information is available on the actions of beta-carboline convu lsants on insect GABA receptors or their potential as insecticides. Ac cordingly, two compounds (3-ethoxy-beta-carboline, 3-EBC; dimethoxy-be ta-carboline-3-methyl ester, DMCM) were studied for their effects on D rosophila melanogaster larval neuron discharge and also in lethality b ioassays on adult female D. melanogaster and adult male Blattella germ anica. Recordings of nerve spiking in the isolated larval central nerv ous system showed that 3-EBC and DMCM inhibited nerve discharge, and t his inhibitory effect was not additive with that of GABA, confirming t hat the inhibition was expressed through an action on the GABA recepto r. Nerve blockage induced by beta-carbolines could not be reversed by picrotoxinin, indicating that there may exist some overlap or negative allosteric coupling between the picrotoxinin and beta-carboline bindi ng sites. DMCM and 3-EBC effectively antagonized the effects of exogen ously applied GABA in nerve preparations from insecticide-susceptible larvae. In contrast, preparations from the rdl strain of D. melanogast er, which possesses a GABA receptor that is highly resistant to cyclod ienes and related convulsants, were less sensitive to the GABA antagon ist effect of DMCM. Neither of the beta-carbolines produced any apprec iable mortality in insects, even when synergized with piperonyl butoxi de or S,S,S-tributyl phosphorotrithioate. The toxicity of the beta-car bolines is probably limited by their relatively weak effects on the GA BA receptor and perhaps also by pharmacokinetic factors. These conside rations, coupled with the cross-resistance observed in cyclodiene-resi stant insects, suggest that the currently available beta-carbolines ar e not viable as lead compounds for insecticide screening efforts.