EFFECT OF NEUROTROPIC AGENTS ON TOTAL PYRIDOXAL PHOSPHATE AND ON THE ACTIVITY OF THE DECARBOXYLASE OF AROMATIC AMINO ACIDS AS WELL AS OF OTHER PYRIDOXAL PHOSPHATE‐DEPENDENT ENZYMES IN RAT BRAIN¹

Abstract

1) Rats received single intraperitoneal injections of various neuroactive chemicals in order to compare the changes of gross behaviour and the level of pyridoxal phosphate as well as the activity of the decarboxylase of aromatic amino acids, of glutamate decarboxylase and of tyrosine transaminase in the brain.(2) The majority of excitatory agents tested (i.e. convulsives like amino-oxyacetate, thiosemicarbazide, pentylenetetrazol and oxotremorine; stimulants such as amphetamine, theophylline and methylphenidate; the amphetamine-like monoamine oxidase inhibitor tranylcypromine as well as the classical monoamine oxidase inhibitor iproniazid when combined with the monoamine releaser Ro 4-1284) caused a decrease in aromatic decarboxylase activity which was coexistent with maximal changes of gross behaviour and partly preceded the latter. The level of pyridoxal phosphate was only partially parallel. As an exception, depression of aromatic decarboxylase was lacking after cocaine (which reduced pyridoxal phosphate only), atropine, the hallucinogens lysergic acid diethylamide and mescaline as well as the combination of the dopamine precursor L-DOPA and the aromatic decarboxylase inhibitor Ro 4-4602.(3) Depression ofobvious central nervous functions was almost regularly accompanied and in part preceded by increase of DCA activity (i.e. with the anaesthetics pentobarbitone, diethy! ether and chloroform, the neuroleptics chlorpromazine, haloperidol, reserpine and the henzoquinolizine Ro 4-1284 as well as the tranquillizers diazepam and chlordiazepoxide). Pyridoxal phosphate was increased during or after maximal behavioural changes by pentobarbitone and chlorpromazine only. As an exception, activation of aromatic decarboxylase was absent after nlorphine.(4) The activity of glutamate decarboxylase was significantly reduced by thiosemicarbazide only, whereas a distinct increase in enzyme activity was exclusively observed after atropine.(5) Tyrosine transaminase activity was significantly diminished by amino-oxyacetate only and showed a late increase after tranylcypromine.(6) It is concluded that there is an inverse relationship, in the majority of neuroactive chemicals tested, between changes of gross behaviour and cerebral aromatic decarboxylase activity. Thereby, the latter is neither regularly related to corresponding variations of the total cerebral pyridoxal phosphate nor to hitherto described alterations of the monoamine turnover nor to effects on other vitamin B,-dependent enzymes.

3-Hydroxykynurenic Acid and Type 2 Diabetes: Implications for Aging, Obesity, Depression, Parkinson’s Disease, and Schizophrenia

“…We could not fi nd studies of the effect of AAD on KMO and P5P. However, typical antipsychotic drug, chlorpromazine, was reported to activate KMO in mouse liver in both in vivo and in vitro studies (Mostafa et al 1982 ) and to cause P5P defi ciency in rat brains (Gey and Georgi 1974 ). The state of P5P deficiency might be further perpetuated by 3-HK and 3H-KYNA-induced inhibition of P5P (Karawya et al 1981 ).…”