However, the precise mechanisms underlying the
psychotropic,
sedative, and
anxiolytic actions of kavain and related kavalactones are still debated. Direct binding to the
benzodiazepine/
flumazenilbinding site of the
GABA-A receptor does not occur with kavain
enantiomers.[3] Many studies involved kava extracts from different plant parts and are, therefore, not applicable to kavain itself. In 2016, kavain was shown to bind at the extrasynaptic α4β2δ GABAA receptor and
potentiateGABA efficacy, similarly to
barbiturates.[4]
A comparative review of
in-vivo studies with kavain (and related kavapyrones) to commonly used
antiepileptic drugs and
mood stabilizers affecting ion fluxes indicates that the kavapyrones are weakly Na+ antagonistic and therefore antiepileptic. They also have pronounced
L- type Ca2+ channel antagonistic properties and act as a positive modulator of the early K+ outward current, which contribute to mood stabilizing properties similar to
lamotrigine.[5]
^Grunze, Heinz; Langosch, Jens; Schirrmacher, Karin; Bingmann, Dieter; Von Wegerer, Jörg; Walden, Jörg (2001). "Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers - a review". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 25 (8): 1555–70.
doi:
10.1016/S0278-5846(01)00208-1.
PMID11642654.
S2CID41325450.
^Rowe, A.; Narlawar, R.; w. Groundwater, P.; Ramzan, I. (2011). "Kavalactone Pharmacophores for Major Cellular Drug Targets". Mini Reviews in Medicinal Chemistry. 11 (1): 79–83.
doi:
10.2174/138955711793564088.
PMID21034404.