cgp-37849 and Dyskinesia--Drug-Induced

The competitive NMDA-antagonists SDZ EAA-494 and CGP 37849 and the mixed D-1/D-2 dopamine agonists CI 201-678 and SDZ 205-152 reverse akinesia in monoamine-depleted mice in a dose dependent manner. Combination of threshold doses of NMDA-antagonists with dopamine agonists markedly enhances anti-akinetic effects. CI 201-678 which in addition to D-1 and D-2 receptors stimulates alpha-2 receptors produces a stronger effect than SDZ 205-152 which is devoid of alpha-2 agonist activity. The results indicate that concomitant blockade of NMDA-receptors and activation of dopamine receptors results in synergistic or at least additive motor stimulatory effects.

Topics: 2-Amino-5-phosphonovalerate; alpha-Methyltyrosine; Animals; Binding, Competitive; Caudate Nucleus; Dopamine Agents; Drug Synergism; Dyskinesia, Drug-Induced; Indoles; Male; Methyltyrosines; Mice; Motor Activity; N-Methylaspartate; Piperazines; Putamen; Receptors, Dopamine; Receptors, N-Methyl-D-Aspartate; Reserpine