Effect of acute administration of antidepressant maprotiline on regional levels of inhibitory and excitatory neurotransmitter amino acids in rat brain

Groups of rats were injected with increasing doses of the antidepressant, maprotiline [0.0, 2.5, 12.5 and 25.0 mg/kg ip]. The dose range corresponded to average human therapeutic dose, loading dose and overdosage levels. The concentrations of glycine [Gly], gamma aminobutyric acid [GABA], taurin [Tau], aspartate [Asp] and glutamate [Glu] in the cortex, hippocampus, midbrain and the cerebellum were determined 2 hr after dosing using gas liquid chromatography. Maprotiline increased the hippocampal level of GABA, the cerebellar levels of ASP and Glu, but otherwise decreased the levels of the estimated amino acids in the different areas tested. The rank order of the response correlated with loci of action of the antidepressants and is in harmony with adverse reactions of overdosing of maprotiline. Changes in brain amino acids were suggested to be involved in the mechanism of action as well as neurotoxic effects of maprotiline probably through modulation of the firing rates of noradrenergic nerve fibers

effect of short term chronic administration of piracetam, maprotiline and their combination on prostaglandin F2 cyclic AMP and hepatorenal functions in rats

Four groups, each of six adult male albino rats received daily the antidepressant maprotiline 13.5 mg/kg, or the nootropic piracetam 450.0 mg/kg, or the combination of both treatments or the vehicle orally for 4 weeks, respectively. Twenty four hours after the last dose, blood samples were obtained for the colorimetric estimation of serum glutamate pyruvate transaminase [GPT], alkaline phosphatase [AP], creatinine and the radioimmunoassay [RIA] of circulating cyclic 3',5' adenosine monophosphate [cAMP] and prostaglandin PGF 2 alpha. Cerebral levels of PGF 2 alpha were also determined by RIA. All treatments did not pathologically change the level of serum GPT, AP or creatinine. However, they potently reduced circulating cAMP by about 90%, but markedly elevated circulating PGF 2 alpha to about 3 folds control values. On the other hand, brain level of PGF 2 alpha was not affected by maprotiline but was elevated by 43% and 128% over control values in response to piracetam and its combination with maprotiline, respectively. It was concluded that this drug combination did not adversely affect the hepatorenal function. The probable role of PGF 2 alpha in the mechanism of the nootropic action of piracetam may indicate that its combined administration with the antidepressant maprotiline may be advantageous but should be carefully monitored

Comparative effects of anti-inflammatory drugs and an anabolic agent on the subcellular components, lysosomal enzymes and oxygen consumption of mitochondria in rat liver

The effect of oral administration of piroxicam in dose 1.8 mg/Kg [L.D] and 5.4 mg/Kg [H.D.], pirprofen in doses 8 mg/Kg [L.D.] and 24 mg/Kg [H.D.] and primobolan in dose 1.8 mg/Kg b.wt for 8 successive weeks, on the total activities and extralysosomal release of B-galactosidase [B-GAL], N-acetyl 8-glucosaminidase [B-NAG] and alpha-galactosidase [alpha-GAL] in rat liver were examined [on 10 groups]. The collective data showed that primobolan and piroxicam by the two doses has no effect on alpha-GAL activity and the enzyme release. B-NAG and B-GAL activities were affected by the high dose of piroxicam and the combined mixture with primobolan. The total enzymatic activity was inhibited, while the extralysosomal release was significantly increased. Primobolan inhibited B-GAL activity, also the low dose of piroxicam in combined mixture suppressed the total enzymatic activity of B-NAG. In addition, the high dose of pirprofen exerted an enhancement on the total enzymatic activity and the extralysosomal release while the low dose of this drug resulted in a significant increase the total activity of B-NAG and release of B-GAL. Comparative studies of the test anti-inflammatory drugs on the O[2]-consumption of rat liver mitochondria showed that the enhancement effect on the respiration, were dose dependent

potentiation of the acute toxicity of niridazole by the concurrent administration of some commonly used insecticides in rats

The oral acute toxicity of niridazole given alone and in combination with 1/100 of the median lethal dose of either carbaryl [Sevin] or malathion was studied in albino rats. Sevin induced a three fold increase in the toxicity of niridazole as shown by the decrease of its LD[50] to one third of its value in normal controls. Besides, the maximal tolerated dose of niridazole was lowered by 50%. Malathion induced a two fold increase in the toxicity of niridazole and a 50% reduction in its maximal tolerated dose