GlycineB antagonists as potential therapeutic agents. Previous hopes and present reality

• Published in: Amino acids 1998, Vol.14 (1-3), p.235-239
• Main Authors: Danysz, W, Parsons, C G, Karcz-Kubicha, M, Schwaier, A, Popik, P, Wedzony, K, Lazarewicz, J, Quack, G
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Excitatory Amino Acid Antagonists - adverse effects; Excitatory Amino Acid Antagonists - pharmacology; Glycine - antagonists & inhibitors; Models, Biological; Neuroprotective Agents - adverse effects; Neuroprotective Agents - pharmacology; Rats; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - chemistry
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/BF01345268

It is not clear what therapeutic application is most likely for agents blocking glycine site of the NMDA receptors (glycineB). Majority of the studies to date used either glycineB antagonists with doubtful brain penetration or partial agonists. Following systemic administration to rats of our newly developed glycineB 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-like effects, lack of anxiolytic activity, inhibition of physical and motivational aspects of morphine dependence and neuroprotective activity in global ischaemia. The side effects include: sedation, ataxia, and myorelaxation. We detected neither vacuolisation in the cingulate cortex nor impairment of pre-pulse inhibition indicating lack of psychotomimetic potential.