ABSTRACT
Hepatic tryptophan 2,3-dioxygenase (TDO) is one of the rate-limiting enzymes in tryptophan catabolism and plays an important role in regulating the physiological flux of tryptophan into relevant metabolic pathways. In this study, we determined the effect of the non-steroidal anti-inflammatory agents, tolmetin and sulindac, on rat liver TDO activity and the subsequent changes in the hippocampal and striatal neurotransmitter levels. The amount of melatonin produced by the pineal gland was also measured using high performance liquid chromatography (HPLC). Treatment of rats with tolmetin or sulindac (5 mg/kg/bd for 5 days) significantly inhibited liver TDO activity. The results show that whilst tolmetin and sulindac increase serotonin levels in the hippocampus, these agents also significantly reduce dopamine levels in the striatum. Tolmetin, but not sulindac, increased the amount of melatonin produced by the pineal gland. The results of this study suggest that whilst tolmetin and sulindac may be beneficial for patients suffering from depression, these agents also have the potential to induce adverse effects in patients suffering with neurological disorders such as Parkinson's disease.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Enzyme Inhibitors/toxicity , Liver/drug effects , Sulindac/toxicity , Tolmetin/toxicity , Tryptophan Oxygenase/antagonists & inhibitors , Animals , Chromatography, High Pressure Liquid , Corpus Striatum/drug effects , Corpus Striatum/enzymology , Dopamine/metabolism , Hippocampus/drug effects , Hippocampus/enzymology , Liver/enzymology , Male , Melatonin/analysis , Melatonin/metabolism , Pineal Gland/chemistry , Pineal Gland/drug effects , Pineal Gland/metabolism , Rats , Rats, Wistar , Serotonin/metabolism , Tryptophan Oxygenase/metabolismABSTRACT
We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs inhibited cyanide-induced superoxide anion generation, as well as lipid peroxidation in rat brain homogenates, the combination of the agents resulting in a potentiation of this effect. Acetaminophen or aspirin when administered alone or in combination, did not alter dopamine (DA) levels in the forebrain or in the striatum. Intranigral infusion of MPP+ in rats caused severe depletion of striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic post-treatment of acetaminophen afforded partial protection, whereas similar treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA depletion. While these findings suggest usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.
Subject(s)
1-Methyl-4-phenylpyridinium/toxicity , Acetaminophen/pharmacology , Analgesics, Non-Narcotic/pharmacology , Aspirin/pharmacology , Dopamine/physiology , Lipid Peroxidation/drug effects , Neurotoxicity Syndromes/prevention & control , Neurotoxins/antagonists & inhibitors , Superoxides/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/antagonists & inhibitors , 1-Methyl-4-phenylpyridinium/antagonists & inhibitors , Animals , Dopamine Agents/toxicity , Male , Neostriatum/drug effects , Neostriatum/metabolism , Neurotoxicity Syndromes/pathology , Nitroblue Tetrazolium , Prosencephalon/drug effects , Prosencephalon/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold-restraint stress-induced ulceration. Secretory studies conducted in pyloric-ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric volume were only observed at the highest dose of the drug. In another set of experiments, when 50% alcohol (v/v) was administered to the pyloric-ligated rats pretreated with amitriptyline, it was observed that the drug significantly reduced the pH, total acidity and protein content.
Subject(s)
Amitriptyline/therapeutic use , Antidepressive Agents/therapeutic use , Muscarinic Antagonists/therapeutic use , Stomach Ulcer/prevention & control , Amitriptyline/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antidepressive Agents/pharmacology , Aspirin/adverse effects , Cold Temperature/adverse effects , Ethanol/adverse effects , Gastric Acid/metabolism , In Vitro Techniques , Indomethacin/adverse effects , Male , Models, Biological , Muscarinic Antagonists/pharmacology , Rats , Stomach Ulcer/etiology , Stomach Ulcer/pathology , Stress, Psychological/complicationsABSTRACT
The methanolic extract of Clerodendrum phlomidis Linn. (MECP) leaves was evaluated for its psychopharmacological activities in several experimental models using Swiss albino mice and Wistar albino rats. The MECP was found to cause significant reduction in spontaneous activity, and decreases in exploratory behavioral profiles by the Y-maze and head dip test. It also showed reduction in muscle relaxant activity by rotarod, 30 degrees inclined screen and traction tests, as well as significantly potentiated the phenobarbitone sodium-induced sleeping time in the doses examined (200, 400 and 600 mg/kg body wt.). All the results were compared with respective controls for the evaluation of significance.
