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INVITED DISCUSSION 
THE ERPECT OF PSYCHOTROBIC DRUGS AND 
CHEMICALLY RELATED SUBSTANCES ON y-AMINOBUTYRIC ACID 
AND GEUTAMIC ACID IN BRAINTISSUE* 
Mee RINSING S*. WE KAR OER **) West Een AUHe Ase: 
HK. OOSTERHUISS ann PP. A. ROUKEMA?* 
Vrije Universiteit, Amsterdam and Research Department Brocades, Amsterdam 
(The Netherlands) 
INTRODUCTION 
Since the discovery of y-aminobutyric acid (GABA) by ROBERTS AND FRANKEL} 
its function and metabolism with respect to the central nervous system has been 
studied at numerous laboratories. Several of these investigations have shown that 
GABA may be of value in controlling the neuron activity”, that it can serve as a 
substrate in oxidative metabolism? and that dysfunction of the GABA system 
occurs in the case of pyridoxine deficiency* °. 
The GABA level in the brain is not affected by high doses administered parenterally ; 
apparently the blood-brain barrier is relatively impermeable to this compound. 
Under certain conditions, however, the GABA level may be changed in vivo. 
Thus a decrease was established, for instance, in the case of hypoglycaemia‘, after 
administration of convulsive hydrazides*, and, in mice, under the influence of re- 
serpine®. An increase was found by HAKKINEN® with alcohol, by WoopBURY AND 
VERNADAKIS® with acetazolamide and by RosBeErts® with hydroxylamine. 
In vitro investigations by TOWER! showed that both the GABA and the L-glutamic 
acid (Glu) level decreased if sliced rat brain cortex was incubated with glucose 
and 2-deoxyglucose as a substrate, and under 10° oxygen; the same effect was 
found with brain slices of epileptics. Malonate increased the amino acid content. 
The influence of varying conditions on level and metabolism of GABA and Glu 
in brain tissue was investigated by ELLIOTT AND VAN GELDER!!, TAKAGAKI ef al.??, 
STERN ef al.13 and others. 
Little is known, however, about the effect of psychotropic drugs on oxidative 
metabolism or on the level of the amino acids mentioned. 
EXPERIMENTAL PART 
We investigated the 7 vitro effect of a large number of psychotropic drugs, on 
oxygen consumption and on the GABA and Glu levels in the tissue and the incuba- 
tion medium}; 15, 16, 
As the Parkinson drug orphenadrine (Disipal ) finds extensive clinical application 

* Presented orally by Dr. Nauta. This is the second part of Biochemical Studies on Psychotropic 
Drugs. For part I see J. Newrochem., 5 (1960) 121. 
** Research Department Brocades, Amsterdam. 
*** Chemical Laboratory Vrije Universiteit, Amsterdam. 
§ Laboratory for Chemical Physiology Vrije Universiteit, Amsterdam. 
References p. 498 
