GLYCINE(B) ANTAGONISTS AS POTENTIAL THERAPEUTIC AGENTS - PREVIOUS HOPES AND PRESENT REALITY

It is not clear what therapeutic application is most likely for agents blocking glycine site of the NMDA receptors (glycine(B)). Majority of the studies to date used either glycine(B) antagonists with doubtful brain penetration or partial agonists. Following systemic administrati on to rats of our newly developed glycine(B) antagonists (MRZ 2/570; 2 /571 and 2/576) and L-701,324 (MSD) as a reference agent the following behavioural effects were observed: weak (if any) antiparkinsonian-lik e effects, lack of anxiolytic activity, inhibition of physical and mot ivational aspects of morphine dependence and neuroprotective activity in global ischaemia. The side effects include: sedation, ataxia, and m yorelaxation. We detected neither vacuolisation in the cingulate corte x nor impairment of pre-pulse inhibition indicating lack of psychotomi metic potential.