Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers - A review

1. Antiepileptic drugs that are successful as mood stabilizers, e.g. carbam azepine, valproate and lamotrigine, exhibit a characteristic pattern of act ion on ion fluxes. As a common target, they all affect Na+- and Ca2+ inward and K+ outward currents. 2. Furthermore, they have a variety of interactions with the metabolism and receptor occupation of biogenic amines and excitatory and inhibitory amino acids, and, by this, also influence long-term potentiation (LTP) to differ ent degrees. 3. The kava pyrones (+/-)-kavain and dihydromethysticin are constituents of Piper methysticum. Anticonvulsant, analgesic and anxiolytic properties hav e been described in small open trials. 4. In the studies summarized in this article the effects mainly of (+/-)-ka vain were tested on neurotransmission and especially on voltage gated ion c hannels. It is assumed that effects on ion channels may significantly contr ibute to clinical efficacy. 5. Experimental paradigms included current and voltage clamp recordings fro m rat hippocampal CA I pyramidal cells and dorsal root ganglia as well as f ield potential recordings in guinea pig hippocampal slices. 6. The findings suggest that (i) kava pyrones have a weak Na+ antagonistic effect that may contribute to their antiepileptic properties (ii) that they have pronounced L- type Ca2+ channel antagonistic properties and act as an positive modulator of the early K+ outward current. These two actions may be of importance for mood stabilization. (iii) Furthermore, kava. pyrones h ave additive effects with the serotonin-1A agonist ipsapirone probably cont ributing to their anxiolytic and sleep- inducing effects. (iv) Finally, the y show a distinct pattern of action on glutamatergic and GABAergic transmis sion without affecting LTP. The latter, however, seems not to be true for t he spissum. extract of Kava where suppression of UP was observed. 7. In summary, kava pyrones exhibit a profile of cellular actions that show s a large overlap with several mood stabilizers, especially lamotrigine.