The incidence of head lice, Pediculus humanus capitis, in the West is increasing, with insecticide resistance the likely cause. Previous studies have explored the utility of essential oils, and some of their constituent monoterpenoids, in the treatment of head lice. This investigation examines the relative short-term toxicity of a range of different monoterpenoid structures on adult clothing lice, Pediculus humanus cmporis, and their eggs; a structure-activity series was generated for the adults, and partially for eggs. The most effective monoterpenoid against adult lice was (+)-terpinen-4-ol, with monocyclic compounds containing a single 0-atom having the highest activities. Furthermore, there appear to be important differences between the relative potencies of monoterpenoids on lice and eggs, as nerolidol was particularly effective against eggs but completely ineffective against adult lice. To investigate the insecticidal mechanism of action of monterpenoids, various pediculicidal structures were screened for activity on an insect ionotropic GABA receptor, composed of the Drosophila melanogaster subunit RDLac, expressed in Xenopus oocytes. Thymol, eugenol and carvacrol potentiated GABA responses at this receptor, and possessed agonist activity at high concentrations. This is the first documentation of monoterpenoid bioactivity at an isolated insect receptor known to be representative of an in vivo insecticidal target. Thymol also had potentiating and agonist effects on human al(33y2s GABAA receptors expressed in Xenopus oocytes, and 50 (AM thymol induced a leftwards shift of the GABA dose-response curve. Further work on this receptor examined the interaction of thymol with previously characterised modulator binding sites. The results of functional studies suggest that thymol does not share a binding site with benzodiazepines, barbiturates, steroids, propofo1,13-carbolines or loreclezole. The direct involvement of insect GABA receptors in monoterpenoid insecticidal activity remains to be confirmed, as does the location of the thymol binding site on insect and mammalian ionotropic GABA receptors.

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Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 29-30).

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