ANTAGONISTS OF THE NMDA RECEPTOR-CHANNEL COMPLEX AND MOTOR COORDINATION

Many structurally different, centrally active antagonists of the NMDA receptor-channel complex induce phencyclidine-like side effects in mammals which include head weaving, body rolling, sniffing and disturbances of motor coordination. The ability of these compounds to cause disturbances of motor coordination correlates directly with their ability to antagonize the NMDA receptor-channel complex in vivo. Although noncompetitive antagonists increase motility in rodents, whereas competitive antagonists do not, both classes of compounds appear to induce schizophrenia-like psychosis in human beings, and cause similar changes in a variety of different biogenic amine neurotransmitter systems in the limbic and motoric areas of the brain. The complex spectrum of behavioural effects observed after the administration of antagonists of the NMDA receptor-channel complex probably reflects the intricate nature of the interaction with positive and negative feedback loops of the motor circuit. Recent research indicates that the site of integration of this interaction could be the striatal medium spiny GABAergic neuron.