The effects of kynurenic acid, quinolinic acid and other metabolites of tryptophan on the development of the high pressure neurological syndrome in the rat.
The effects of some biologically active metabolites of tryptophan on the high pressure neurological syndrome (HPNS) were studied. Kynurenic acid, quinolinic acid, 5-hydroxytryptophan, kynurenine and 3-hydroxyanthranilic acid, at doses within the physiological range, were administered exogenously to rats prior to exposure to increased pressure and any effects on the tremor, myoclonus and convulsion end points of the high pressure neurological syndrome were observed. Quinolinic acid (25 and 50 mg/kg) and kynurenine (50 mg/kg) reduced the onset pressure for tremor, but not myoclonus or convulsions. Kynurenic acid (100 mg/kg) increased tremor onset pressure; 5-hydroxytryptophan (20 mg/kg) slightly increased onset pressure for tremor but decreased that for myoclonus. 3-Hydroxyanthranilic acid (20 mg/kg) had no significant effect on any of the motor signs of the syndrome. These data provide further support for the idea that the motor events seen in the high pressure neurological syndrome are not produced by a single mechanism. Differences between the responses to related metabolites suggest that the precise balance between compounds such as kynurenic acid and quinolinic acid may be important in the appearance of the high pressure neurological syndrome.
Wardley-Smith
B
B
HPNS Group, Clinical Research Centre, Harrow, Middlesex, U.K.
Halsey
M J
MJ
Hawley
D
D
Joseph
M H
MH
D000818:Animals; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D006610:High Pressure Neurological Syndrome / Q000503:physiopathology*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism*
D011725:Pyridines; D011805:Quinolinic Acids; D014364:Tryptophan; D007736:Kynurenic Acid