Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels

Dairam, A. and Antunes, Edith Martins and Saravanan, K.S. and Daya, S. (2006) Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sciences, 79 (24). pp. 2269-2274. ISSN 0024-3205

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Official URL: http://dx.doi.org/10.1016/j.lfs.2006.07.028

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.

Item Type:Article
Uncontrolled Keywords:Tolmetin; Sulindac; Tryptophan 2,3-dioxygenase; Serotonin; Dopamine; Melatonin; Parkinson's disease; NSAIDS
Subjects:Y Unknown > Subjects to be assigned
Divisions:Faculty > Faculty of Pharmacy
ID Code:471
Deposited By: Mrs Eileen Shepherd
Deposited On:22 Nov 2006
Last Modified:01 Aug 2012 07:16
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