Kawain CAS NO.500-64-1

Effects of kawain and dihydromethysticin on field potential changes in the hippocampus.[Pubmed: 9194150]

Prog Neuropsychopharmacol Biol Psychiatry. 1997 May;21(4):697-706.

1. The kava-pyrones Kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties.
METHODS AND RESULTS:
3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 mumol/l and 10 to 40 mumol/l, respectively. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 mumol/l Kawain and 10 mumol/l dihydromethysticin indicated additive actions of both drugs. 5. Since the serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of Kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining Kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively.
CONCLUSIONS:
6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components Kawain and dihydromethysticin may enhance the effects of the anxiolytic serotonin-1A agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.

Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro.[Pubmed: 16033948]

Drug Metab Dispos. 2005 Oct;33(10):1555-63.

METHODS AND RESULTS:
The oral pharmacokinetics of the kavalactone, Kawain (100 mg/kg), were determined in rats with and without coadministration of kava extract (256 mg/kg) to study the effect of the extract on drug disposition. Kawain was well absorbed, with >90% of the dose eliminated within 72 h, chiefly in urine. Compared with Kawain alone, coadministration with kava extract caused a tripling of Kawain AUC(0-8 h) and a doubling of C(max). However, a 7-day pretreatment with kava extract (256 mg /kg/day) had no effect on the pharmacokinetics of Kawain administered on day 8.
CONCLUSIONS:
The 7-day pretreatment with kava extract only modestly induced hepatic P450 activities.

Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors.[Pubmed: 25098935]

Planta Med. 2014 Aug;80(12):1001-8.

Kawain, methysticin, and dihydromethysticin, all belonging to the group of kavalactones, were identified as advanced glycation endproduct inhibitors.
METHODS AND RESULTS:
With IC50 values of 43.5 ± 1.2 μM and 45.0 ± 1.3 μM for Kawain and methysticin, respectively, the compounds inhibited the in vitro protein glycation significantly better than aminoguanidine (IC50 = 231.0 ± 11.5 μM; p = 0.01), an established reference compound. Kawain and methysticin also inhibited the formation of dicarbonyl compounds, which are intermediates in the process of advanced glycation endproduct formation.
CONCLUSIONS:
Similarly, Kawain and aminoguanidine prevented the formation of thiobarbituric reactive substances in both low-density lipoprotein and linoleic acid oxidation. Moreover, Kawain and aminoguanidine prevented advanced glycation endproduct formation by chelating Fe(3+) and Cu(2+) two to three times better than aminoguanidine. Furthermore, Kawain increased the mean life span of Caenorhabditis elegans exposed to high glucose.