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PACIFIC SCIENCE, Vol. XXII, July 1968 
same dose of hexobarbital sodium for 27 hours. 
Enhancement of barbiturate narcosis is a prop- 
erty which is shared by a relatively large num- 
ber of substances with central sedative prop- 
erties. What is very impressive in the case of 
DHM, however, is the magnitude of the effect. 
ANALGETIC effect: Together with Briig- 
gemann, a team under K. H. Meyer in the 
Pharmacological Institute of the University of 
Freiburg tested the analgetic effectiveness of the 
two kawa pyrones, DFIK (dihydrokawain) and 
DHM. In the analgesic test according to Gross 
these two substances prove to be comparable in 
effect with dimethylaminophenazone. These 
results are summarized in Table 2. 
local anesthetic properties: I have men- 
tioned earlier that chewing crude kawa anes- 
thetizes the tip of the tongue. This anesthetic 
effect is caused by DHK, a fact which has been 
known for a long time (van Veen, 1938). 
Again it was H. J. Meyer and his collaborators 
who carried out the detailed study of the local 
anesthetic properties using the testing methods 
of scientific pharmacology. It was shown, first, 
that not only DHK but that all the other kawa 
pyrones possess local anesthetic properties; how- 
ever, not all pyrones have an equally strong 
effect. It was further demonstrated that the 
pyrones developed superficial anesthetic as well 
as infiltration effects. I shall mention a few de- 
tails of the experiment on surface anesthesia 
(rabbit cornea) and the results. Most effective 
with respect to the degree of hydrogenation are 
the A 5 -dihydro derivatives, followed by the 
A 5,7 -tetrahydro derivatives; the non-hydro- 
genated yangonin homologues are ineffective. 
Unsubstituted derivatives are more effective than 
dioxymethylene substituted ones. Accordingly, 
TABLE 2 
Relative Analgetic Effect of DHM and DHK 
(Condensed from Briiggemann and Meyer, 1963) 
ANALGETIC AGENT 
DOSE (mg/kg) 
morphine 
2.5 
dimethylaminophenazone 
100 
dihydrokawain 
120 
dihydromethysticin 
140 
acetylsalicylic acid (aspirin) 
200 
the most effective compound in surface anes- 
thesia is kawain which equals the effect of 
cocaine in the cornea test. Kawain and cocaine 
possess the same limiting concentration (equal 
to the smallest concentration which causes com- 
plete anesthesia in all animals) and equal 
length of anesthesia. The kawa pyrones are 
somewhat less effective in infiltration anesthesia. 
Of some interest for their evaluation is the fact 
that the kawa pyrones are very compatible with 
tissues and no danger of toxic resorption exists. 
anticonvulsive effects: A cursory com- 
parison of the total effect of kawa on man and 
of the pharmacological activity of the pyrones 
in the animal shows that kaiva acts predominant- 
ly by central paralysis. In order to characterize 
in greater detail substances having a central 
paralytic effect, it is important to know toward 
which central nervous system (CNS) stimulants 
these substances act as antagonists. Furthermore, 
one needs to know whether they are capable of 
inhibiting tonic or clonic spasm components 
of electric shock. 
Concerning the inhibition of electric shock, 
a whole series of well known and excellent 
drugs have been introduced into therapy and 
are frequently used as sedatives which inhibit 
at a given dose but which are toxic. A well 
known example of the statement that CNS 
sedatives are not necessarily effective inhibitors 
of electric stimulation is meprobamate. Other 
sedatives enhance, contrary to expectation, even 
the readiness for contraction; an example is 
reserpine. According to investigations, which 
again were carried out by the Freiburg team, 
DHM and DHK are contraction inhibitors. This 
inhibitory effect is qualitatively and quantita- 
tively comparable with that of phenobarbital, 
pyrimidone, or diphenylhydantoin. Animal ex- 
periments have shown that DHM in particular 
may be considered a strongly effective anti- 
convulsant. 
The behavior of the two kawa pyrones is 
peculiar toward chemical convulsive toxins, 
toward bemegride, pentetrazole, picrotoxin, and 
strychnine. Figure 7 shows the following: (i) 
Tonic bemegride and pentetrazole convulsions 
are activated within a given dose range (pre- 
administration of 20-45 mg/kg DHM). (ii) 
Tonic picrotoxin and strychnine convulsions are 
