Picolinic, kynurenic, xanthurenic and
anthranilic acids are metabolites of L-
kynurenine which, when administered intraperitoneally (i.p.) antagonized (in descending order of potency) the
seizures induced by intracerebroventricular (i.c.v.)
injections of l-
kynurenine sulfate in SHR and C57BL/6 mice. Picolinic and
anthranilic acids were also effective after
oral administration.
Picolinic acid completely prevented
seizures.
Kynurenic acid, when injected i.c.v. prior to l-
kynurenine sulfate, appeared to be more effective than after i.p. administration while picolinic and
anthranilic acids were less effective. This suggest that the antikynurenine effect of metabolites of
kynurenine (kynurenines) is related to different brain structures, i.e.
kynurenic acid predominantly affects structures adjacent to ventricles (e.g. hippocampus, caudate nucleus) while picolinic and
anthranilic acids act on other brain structures or the periphery. Xanthurenic, kynurenic and
picolinic acids merely prolonged the latency of
seizures induced by i.c.v.
quinolinic acid (another metabolite of
kynurenine) or by subcutaneous
strychnine sulfate and i.p.
pentylenetetrazole, and did not modify
seizures induced by i.p.
caffeine and
thiosemicarbazide. This selective antagonism of the tested kynurenines against
kynurenine might be an important
anticonvulsant factor in
kynurenine-dependent
seizures. It is suggested that increased excretion of xanthurenic, kynurenic and
picolinic acids in patients with convulsive states may be manifestations of compensatory processes.