NMDA antagonists: antiepileptic-neuroprotective drugs with diversified neuropharmacological profiles.
In conclusion, NMDA antagonists as anticonvulsants are especially active in preventing the generalization of the behavioural and electrical seizures and display a typical spectrum of in vitro antiepileptiform activities. In addition, based on in vitro and in vivo limbic kindled studies, the drugs should be regarded more as an antiepileptiform than as an anticonvulsant drugs. As neuroprotective drugs, NMDA antagonists are effective against many types of neuronal injury and show a window of activity which does not exceed 1-2 h, thus suggesting an influence of NMDA receptors in the 'early' or 'acute' mechanisms of brain damage. Among NMDA antagonists, glycine antagonists or the morphinans dextromethorphan and dextrorphan showed a spectrum of antiepileptiform and neuroprotective activities broader than other NMDA antagonists. The primary pharmacological activities of NMDA antagonists are accompanied by some effects including perturbation of many sensory, psychological or motor processes. Typical behavioural and EEG changes were also induced by the drugs. In spite of the side-effects elicited by the drugs, differential effects detected among the various classes of NMDA antagonists (i.e. lack of induction of typical EEG-behavioural effects and of typical cortical neurotoxicity) might render some of these suitable for full clinical application as anticonvulsant-neuroprotective drugs.
Sagratella
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Laboratorio di Farmacologia, Istituto superior di Sanità, Roma, Italy.
D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009480:Neuropharmacology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007649:Ketamine