EFFECTS OF KAWAIN AND DIHYDROMETHYSTICIN ON FIELD POTENTIAL, CHANGES IN THE HIPPOCAMPUS

1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 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 hippoca mpal slice preparation of guinea pigs. These 4 are generated by an act ivation of NMDA receptors and voltage dependent calcium channels. 3. K awain and dihydromethysticin reduced reversibly the frequency of occur rence of fp in a concentration range from 5 to 40 mu mol/l and 10 to 4 0 mu mol/l, respectively. 4. Reduction of the fp frequency after addit ion of subthreshold concentrations of 5 mu mol/l kawain and 10 mu mol/ l dihydromethysticin indicated additive actions of both drugs. 5. Sinc e the serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combi ned 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 t he baseline value, respectively. 6. The findings suggest that (i) sing le constituents of Piper methysticum may have additive actions, (ii) t hat the two components kawain and dihydromethysticin may enhance the e ffects of the anxiolytic serotonin-1A agonist ipsapirone and (iii) tha t activation of NMDA receptors and/or voltage dependent calcium channe ls may be involved in the elementary mechanism of action of some kava- pyrones.