M. J. E. Ernsting

THE EFFECT OF PSYCHOTROPIC DRUGS ON γ‐AMINOBUTYRIC ACID AND GLUTAMIC ACID IN BRAIN TISSUE

SOME time ago, one of us (DE WAART, 1956, 1958) published the results of an investigation of the inhibitory effect of a number of diphenhydraminef derivatives on intermediary metabolism. Like the barbiturates, diphenhydramine reduces the oxygen consumption during the aerobic metabolism of rat brain slices (glucose as substrate). The compounds studied at the time mainly consisted of alkyl derivatives of diphenhydramine. Generally speaking, these derivatives display a more pronounced inhibitory effect than diphenhydramine itself. It was also found that some compounds examined affected the amino acid metabolism. By paper chromatography it was demonstrated that at the end of the experiments the concentration in the incubation fluid of some of the amino acids which are released initially (McLwm, 1959) remained at a high level, whereas in the blanks these acids were regained by the tissue. After ninhydrin coloration the chomatograms showed four bands, two of which were particularly distinct. These were identified at the time as glutamic acid and methionine. Barbiturates did not have this effect on the amino acid pattern of the incubation fluid. Of the compounds investigated, orphenadrine (,!I-dimethylaminoethyl-2-methylbenzhydrylether, Disipal @) produced the strongest effect. The pharmacological properties of orphenadrine are very different from those of diphenhydramine. (It has a strongly reduced antihistamine action and a strongly increased atropine one.) The preparation is used for treating Parkinsonism, and recent investigations (SCHEURLE, 1957; ROBITSCHER, 1958; PFEIFFER, 1959) show that it also has psychotropic prop-ties. These observations prompted us to study the effect of psychotropic drugs on amino acid metabolism also. A preliminary note on the results of this investigation was published by us some time ago (NAUTA et al., 1958).

The effect of orphenadrine hydrochloride on the acetylcholine concentration in rat brain

The effect of orphenadrine hydrochloride on the concentration of acetylcholine in the rat brain was investigated. An i.p. dose of 50mgkg caused a significant reduction of the acetylcholine concentration, as shown by determinations at 15 min—where the effect was maximal—and at 30 and 60 min after administration. These findings are discussed in relation to the orphenadrine concentration in the rat brain as a function of time and to other effects of the compound on brain biochemistry as previously established.