CHLORMETHIAZOLE ATTENUATES THE DERANGEMENT OF SENSORY EVOKED-POTENTIAL (SEP) INDUCED BY ICV ADMINISTRATION OF NMDA

Administration to anaesthetized rats of N-methyl-D-aspartate (NMDA 30 nmol ICV) induced a profound derangement of stimulation evoked potenti al (f-SEP) and also autonomic excitation with an increase in arterial blood pressure and heart rate. These effects were antagonised by pretr eatment with dizocilpine (0.5 mg/kg IV). Pretreatment with chlormethia zole (20 mg/kg IV 26 min before NMDA) also markedly diminished the der angement of f-SEP. At the end of the registration period 2 h after NMD A the SEP had recovered to 72.7 +/- 3.4 (% of control; mean +/- SEM) i n saline-treated rats as compared to 96.1 +/- 5.6% in chlormethiazole treated animals (P < 0.01). In contrast to dizocilpine, chlormethiazol e alone had no effect on heart rate or blood pressure and did not alte r the autonomic effects of ICV NMDA. These results demonstrate that ch lormethiazole can antagonise some NMDA-receptor mediated functions, ev en though there is no evidence that it is an NMDA antagonist.