496 W. TH. NAUTA et al. 
son drugs refuted this assumption. The results have been summarised in Table IT: 
Artane 8, Kemadrin® and Pagitane ®, which have closely related structures (see 
Fig. 1), hardly influence the oxygen consumption, while giving little, if any, re- 
sorption of GABA and Glu. Cogentin ® and orphenadrine likewise prevent resorption 
of the amino acids, but in this case the oxygen consumption is inhibited by 60 and 
88%, respectively. 
It is further clear from Table III and Fig. 2 that small structural variations 
result in highly different effects. 
Of the azabenzhydrylethers given in the table, the unsubstituted compound 
TABLE III 
THE INFLUENCE OF SOME AZABENZHYDRYLETHERS ON THE METABOLISM 
OF RAT BRAIN CORTEX in vitvo 




Ti %O, GABA level (ug/r0o mg) Glu level (ug/roo mg) 
Conditions* wie inhi- - = 
(min) bition Medium Tissue Total Medium Tissue Total 
fe) LOO MIZ5 = 23-1 GLA 58:2 eZee 
Control 60 = 1-3) | 2Ol0) 82.0) 23578 sez LOOLG) 
RI R,=R,=H 60 20 1.3 -20.4 21.7 31.2 158-4 TSeQs0 
| 
[" ign Jk 
NAVE 
| | 
R R, =H \ 5 = 
i : iy ah | 60 15 [2 20:8 22:0 40:5) 042:0uESes5 
CH, 
| 
CEH. 
a ea Calalte 60 LOM E2220 4.0) 2051 1285.8) 3424) 320-2 
a 
Hic CH, 

* The concentration of the drugs was 2 m/W/. Glucose was used as a substrate (concentration : 
0.02 M). Metabolism took place under air, with a phosphate buffer which did not contain Ca. 
After dissection we found in the cortex 22.0 wg/100 mg for GABA and for Glu 177.4 uwg/100 mg. 
(RouKEMA!®.) 
and the 2,6-diethyl derivative hardly affect the oxygen consumption, while GABA 
and Glu resorption are found after the former compound only. In the latter case the 
quantity of amino acid in the medium even far exceeds that found after dissection of 
control animals. 
Like Tower! we found that a highly reduced oxygen consumption is attended 
with GABA and Glu depletion of the tissue. However, in our case, the rise found 
for the incubation medium was much higher than was established by Tower. This 
may be due to the fact that we used chopped brain instead of the slices used by 
this investigator. Undoubtedly, the disturbed energy supply plays an important 
part, as was found by STERN et al.3 and others. However, this does not account for 
the rise in the GABA and Glu level. 
References p. 498 
