Strychnine-insensitive
glycine site is one of a few binding sites of
NMDA receptor complex. The aim of these study was to find out whether compounds regarded as
glycine antagonists-
kynurenic acid (KA),
7-chlorokynurenic acid (7-CKA),
5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the
NMDA receptor antagonist,
CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced
seizures and increased the
anticonvulsant effect of
CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and
5,7-DCKA.
D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of
clonidine; the antiakinetic effect of
L-DOPA was enhanced by 7-CKA and
5,7-DCKA, but not by KA. KA and 7-CKA did not change the
spiperone-induced
catalepsy but they attenuated the anticataleptic effect of
CGP 37849; the studied drugs did not change the anticataleptic effect of
MK-801. 7-CKA given icv did not influence the
spiperone-induced
catalepsy as well as the anticataleptic effect of
CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with
imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs
imipramine alone or
glycine antagonist alone); in the case of joint injection with
citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between
glycine antagonists (
kynurenine derivatives) and
CGP 37849 and to the possibility of positive cooperation between the
NMDA- and
glycine-sites antagonists.