Benz(F)isoquinolines as excitatory amino acid antagonists: An indication of their mechanism of action?

Using the technique of microelectrophoresis on cat and rat spinal neurones, the bridged benz(f)isoquinoline, LY154045, like ketamine and dextrorphan, was found to be a selective antagonist of N-methylaspartate, an amino acid used for characterizing excitatory amino acid synaptic receptors. The unbridged analogue, LY154005, was inactive as an amino acid antagonist. This result correlates well with the ability of LY154045, but not LY154005, to displace phencyclidine from CNS tissue and to mimic phencyclidine in behavioural tests. The potential role of N-methylaspartate antagonism in the aetiology of some of the behavioural effects of LY154045, phencyclidine and related drugs is considered.