Effect of chronic treatment with (+)-PHNO, a D2 agonist in MPTP-treated monkeys.
A group of four drug naive Macaca fascicularis were rendered parkinsonian with the neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine and then treated chronically with (+)-PHNO, a potent D2 agonist. After several days, dyskinesia appeared in all animals. At this point, the daily dose of (+)-PHNO was replaced by a dose of the D1 agonist CY 208-243. The substitution by CY 208-243 reproduced the same dyskinesia observed with (+)-PHNO. The administration of the DA synthesis inhibitor AMPT (alpha-methyl-p-tyrosine methyl ester) blocked the dyskinetic and antiparkinsonian effect of (+)-PHNO, and those effects were reestablished by the addition of a subthreshold dose of CY 208-243. Our results show that a selective D2 agonist is capable of inducing dyskinesia and suggest some kind of cooperation between D1 and D2 receptors in the antiparkinsonian and dyskinetic effect produced by (+)-PHNO.
Gomez-Mancilla
B
B
Centre de recherche en neurobiologie, Hôpital de l'Enfant-Jésus, Quebec City, Canada.
Bédard
P J
PJ
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D010617:Phenanthridines / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007211:Indoles; D010078:Oxazines; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C054531:CY 208-243; C042631:naxagolide