Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity

Connick, J.H., Heywood, G.C., Sills, G.J., Thompson, G.G., Brodie, M.J. and Stone, T.W. (1992) Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity. General Pharmacology: The Vascular System, 23(2), pp. 235-239. (doi: 10.1016/0306-3623(92)90017-E) (PMID:1639238)

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Abstract

1. Nicotinylalanine is an analogue of kynurenine which has been reported to inhibit the enzymes kynurenine hydroxylase and kynureninase. 2. In the present study rats were given a tryptophan load together with nicotinylalanine two hours before killing, and the brain, liver and kidneys analysed by HPLC for their kynurenic acid content. 3. Tryptophan alone produced a significant elevation of kynurenate but with the additional administration of nicotinylalanine, levels rose dramatically, including a 19-fold increase in brain. 4. In mice the same dose of nicotinylalanine reduced the incidence of seizures induced by leptazol or electroshock treatment. 5. Since kynurenic acid is an antagonist at excitatory amino acid receptors the results may herald a new approach to producing a pharmacological blockade of amino acid receptors in the brain.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin and Stone, Professor Trevor and Sills, Dr Graeme
Authors: Connick, J.H., Heywood, G.C., Sills, G.J., Thompson, G.G., Brodie, M.J., and Stone, T.W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:General Pharmacology: The Vascular System
Publisher:Elsevier
ISSN:0306-3623
ISSN (Online):1879-0011

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