Effects of newly developed excitatory amino acid antagonists on vestibular type I neurons in the cat.
A newly synthesized compound NC-1200 (oxazolidinone) has been shown to have a powerful inhibitory action on the glutamate response at the neuromuscular junction in crayfish where glutamate is thought to be an excitatory neurotransmitter. However, the pharmacological function of NC-1200 in the CNS of mammals remains unknown. We examined the glutamate blocking action of NC-1200 on various glutamate receptors of cat's vestibular neurons. The effects of NC-1200 on secondary vestibular neurons were studied by intra-venous (3-5 mg/kg) and iontophoretic application using multi-barreled electrodes filled with NMDA, kainic acid and NC-1200 in decerebrated cats. After identification of type 1 neurons, the chemicals were applied to examine their effects on neuronal activity. The results were as follows; i) Systemic application of NC-1200 suppressed type 1 responses to yaw rotation; ii) both NMDA-mediated and kainate-mediated excitations on the vestibular neurons were abolished by application of NC-1200; iii) the suppression of various glutamic receptors was dose-dependent; and iv) the kainate receptor was more strongly suppressed than the NMDA receptor by NC-1200.
Furuya
N
N
Department of Otolaryngol, Ichihara Hospital, Teikyo Univ School of Medicine, Japan.
Koizimi
T
T
Sebata
H
H
D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007478:Iontophoresis; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000494:pharmacology; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D023303:Oxazolidinones; D017470:Receptors, Glutamate / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012399:Rotation; D014725:Vestibular Nerve / Q000187:drug effects*; D014726:Vestibular Nuclei / Q000166:cytology / Q000187:drug effects
D001381:Azepines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D009125:Muscle Relaxants, Central; D016202:N-Methylaspartate; D018377:Neurotransmitter Agents; D010080:Oxazoles; D023303:Oxazolidinones; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C051400:MLV 6976