298 
PACIFIC SCIENCE, VoL XXII, July 1968 
yang on i n 
Fig. 5. Biosynthetic scheme for the formation 
precursor. 
kawain, no long conjugated system is inter- 
rupted when the 7,8-double bond is reduced. 
The dihydrokawain derivatives indeed occur 
in nature. 
Physiological Activity of Kawa Pyrones 
The most intensive study of the pharmacology 
of the kawa pyrones has been carried out for 
some ten years by a team at the Pharmacological 
Institute of the University of Freiburg under the 
direction of H. J. Meyer. The most important 
observations on the effects of the kawa pyrones 
seem to be the following: intensification of 
barbiturate narcosis (Klohs et. al., 1959; Meyer, 
1962) ; analgetic effect (Briiggemann and 
Meyer, 1963) ; local anesthetic properties 
(Meyer and May, 1964) ; anticon vulsive effects 
(Meyer, 1964; Meyer and Meyer-burg, 1964; 
Kretzschmar and Meyer, 1965) ; spasmolytic 
effect (Meyer, 1965^) ; antimycotic effects 
(Hansel, Weiss, and Schmidt, 1966). 
I should like to make another general obser- 
vation on the relationship between pharmacody- 
namic activity of the different kawa pyrones 
and their constitution. As far as animal experi- 
ments are concerned the lactones of the yangonin 
type, that is the dienolides, seem to be — within 
the usual dosages and as compared with enolides 
— pharmacodynamically inert. 
flavokawin A 
of yangonin and a C-15 chalcone from a common 
In the enolides the effective optimum varies 
as a function of the hydrogenation of the 
double-bonded carbon 7 and of substitution in 
the benzene ring together with a dependence on 
the method of testing. For example kawain has 
the strongest effect as a local anesthetic, dihy- 
dromethysticin as a spasmolytic, and dihydro- 
kawain as an intensifier of narcosis. 
INTENSIFICATION OF BARBITURATE NARCOSIS 
(Klohs et al., 1959; Meyer, 1962): When a 
pharmacologist has the task of testing pharma- 
cologically little investigated substances for cen- 
tral sedative properties, he will probably mea- 
sure first the toxicity of the substance and then 
the decrease in spontaneous motility. At a very 
early stage of the screening process he will check 
whether and in which way his substances will 
influence the effect of barbiturates. Substances 
with a central paralyzing effect intensify the 
effect of barbiturates and/or considerably pro- 
long the effect. Dihydromethysticin (DHM) 
possesses to a particularly high degree this effect 
of intensifying barbiturate effects (intensifying 
narcosis). Let me cite an example (Meyer, 
1962). After application of 150 mg/kg of 
hexobarbital sodium, white mice sleep on the 
average for 2 hours. If the animals are pretreated 
with 240 mg/kg DHM, they sleep after the 
