Modulation of Ionotropic GABA Receptors by Natural Products of Plant Origin

Abstract

Publisher Summary This chapter discusses the modulation of ionotropic γ‐aminobutyric acid (GABA) receptors by natural products of plant origin. There is an impressive array of natural products that are known to influence the function of ionotropic receptors for GABA, the major inhibitory neurotransmitter in the brain. The major chemical classes of such natural products are flavonoids, terpenoids, phenols, and polyacetylenic alcohols. The interaction of flavonoids with benzodiazepine modulatory sites on GABAA receptors lead to the great interest in flavonoids as positive modulators of such receptors, many of the interactions between flavonoids and GABAA receptors do not involve classical flumazenil‐sensitive benzodiazepine sites. There are significant synergistic interactions between some of these positive modulators such as between substances isolated from Valeriana officinalis. Thus, the sleep inducing effects of hesperidin are potentiated by 6‐methylapigenin, while the sedating and sleep inducing effects of valerenic acid are potentiated when co‐administered with the flavonoid glycoside linarin. The discovery of second order positive modulators adds new dimension to the concept of the allosteric modulation of GABAA receptors. Second order positive modulators act only in conjunction with a specific first order positive modulator.