Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity.
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.
Connick
J H
JH
Department of Pharmacology, University of Glasgow, Scotland.
Heywood
G C
GC
Sills
G J
GJ
Thompson
G G
GG
Brodie
M J
MJ
Stone
T W
TW
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D004597:Electroshock; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009525:Niacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D014364:Tryptophan / Q000494:pharmacology
D000927:Anticonvulsants; C071261:nicotinylalanine; D009525:Niacin; D014364:Tryptophan; D007736:Kynurenic Acid; D000409:Alanine; D010433:Pentylenetetrazole