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January 2022

Kava-Kava [Piper methysticum G. FORSTER] in modern drug research

Abstract: Recently numerous reviews on Kava-Kava have been published. Contrary to the ethnomedical and pragmatic-therapeutic oriented articles the article presented here concentrates on the importance of isolated Kava-Kava constituents as potential antiepileptics. This review analyzes the results of several doctoral theses, which have not yet been published in commonly accecible journals. In rhizomes and stems of Piper methysticum besides the familiar Kava-pyrone and chalkone pigments dimeric yangoin-derivatives are found besides very small amounts of stigmastendion and an oxaporphinal-alkaloid (cepharadion A). The total Kavaextract as well as the isolated Kava-pyrones have a protecting effect against convulsions induced by poisons and electrical current. In clinical phase 11 trials extract and methysticin were effective in major clonic-tonic seizures, but exerted undesired effects when applied long-termly or in high doses, requirng the discontinuation of the trial. Synthetic variations of methysticin, according to the results of pharmacological tests, appear to be unqualified as antiepileptics. Piperolide, isolated from Piper sanctum is a variaton of methysticin and at all dosages exerts an anticonvulsive effect. Also with respect to the duration of the anticonvulsive effect piperolide is superior to methysticin. Fadyenolide, isolated from Piper fadyenii represents a piperolide shortened by a C2-chain. Pharmacological studies have not begun. Synthetic variations of the dihydro-derivative of fadyenolide have anticonvulsive properties. One of these variations has also proved to be well active as an antiepileptic in clinical trials. Kava-pyrones act as sodium channel blockers. Their antiepileptic effect could therefore, similar to that of phentoin and of other antiepileptics, be based on a decrease of the conductivity of certain cerebral areas. Recent investigations have shown, that Kava-pyrones at low concentrations (IC50 = 2-6 ÁM) bind to the histamine-H3-receptors. Because H3-antagonists are known to exert anticonvulsive effects the addition of H3-antagonism should contribute to the anticonvulsive and antiepileptic effect of Kava-pyrones and chemically related substances.

Keyword(s): Kava- Kava. Piper methysticum

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