Dopamine agonists potentiate antiakinetic effects of competitive NMDA-antagonists in monoamine-depleted mice.
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.
Kannari
K
K
Preclinical Research, Sandoz Pharma, Basle, Switzerland.
Markstein
R
R
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000187:drug effects / Q000503:physiopathology; D015259:Dopamine Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008781:Methyltyrosines / Q000633:toxicity; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012110:Reserpine / Q000633:toxicity; D019805:alpha-Methyltyrosine
D015259:Dopamine Agents; D007211:Indoles; D008781:Methyltyrosines; D010879:Piperazines; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016202:N-Methylaspartate; D019805:alpha-Methyltyrosine; D015763:2-Amino-5-phosphonovalerate; C047807:CI 201-678; C070723:SDZ 205-152; D012110:Reserpine