A STUDY OF THE N-METHYL-D-ASPARTATE ANTAGONISTIC PROPERTIES OF ANTICHOLINERGIC DRUGS

Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex hav e the ability to terminate nerve agent-induced seizures and modulate t he neuropathologic consequences of agent exposure. Drugs with mixed an ticholinergic and anti-NMDA properties potentially provide an ideal cl ass of compounds for development as anticonvulsant treatments for nerv e agent casualties. The present experiment evaluated the potential NMD A antagonist activity of 11 anticholinergic drugs by determining wheth er pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antago nized NMDA lethality and are ranked according to their potency: mecamy lamine > procyclidine = benactyzine > biperiden > trihexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinu clidinyl benzilate (QNB), and scopolamine failed to show NMDA antagoni st properties. In addition, and unexpectedly, diazepam, ethanol, and p entobarbital were also shown to be capable of antagonizing NMDA lethal ity over a certain range of doses. The advantages and limitations of u sing antagonism of NMDA lethality in mice as a bioassay for determinin g the NMDA antagonist properties of drugs are also discussed.