Antitussive agents as N-methylaspartate antagonists: further studies.
The relative potencies of ketamine and the morphinan derivatives dextrorphan, dextromethorphan, and levorphanol as antagonists of the excitatory actions of N-methylaspartate on rat spinal neurones in vivo were examined, both following their microelectrophoretic administration and, with the exception of levorphanol, after intravenous injection. Applied microelectrophoretically, dextrorphan was a more potent N-methylaspartate antagonist than ketamine, levorphanol, or dextromethorphan. After systemic administration, however, dextrorphan was rather less potent than ketamine in this respect, whereas dextromethorphan remained less potent than either ketamine or dextrorphan. Noscapine, an antitussive that lacks anticonvulsant activity, failed to reduce selectively responses to N-methylaspartate as did papaverine, an isoquinoline structurally related to noscapine, and triprolidine, an antihistamine commonly found in proprietary cough medicines. The results are discussed with particular reference to the potential of the compounds tested as anticonvulsant and neuroprotective agents in vivo.