Experimental laboratory study
Effects of kawain and dihydromethysticin on field potential changes in the hippocampus

https://doi.org/10.1016/S0278-5846(97)00042-0Get rights and content

Abstract

  • 1.

    1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties.

  • 2.

    2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg2+, recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels.

  • 3.

    3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 μmol/1 and 10 to 40 μmol/1, respectively.

  • 4.

    4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 μmol/1 kawain and 10 μmol/1 dihydromethysticin indicated additive actions of both drugs.

  • 5.

    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.

  • 6.

    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.

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