Effect of chronic treatment with (+)-PHNO, a D2 agonist in MPTP-treated monkeys.

Abstract

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.

• Authors: B Gomez-Mancilla, P J Bédard
• Journal: Experimental neurology (Exp Neurol) Vol. 117 Issue 2 Pg. 185-8 (Aug 1992) ISSN: 0014-4886 [Print] United States
• PMID: 1354166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Dopamine Agents
• Indoles
• Oxazines
• Phenanthridines
• Receptors, Dopamine
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• CY 208-243
• naxagolide

Topics

• Animals
• Antiparkinson Agents (pharmacology)
• Dopamine Agents (pharmacology)
• Female
• Indoles (pharmacology)
• MPTP Poisoning
• Macaca fascicularis
• Motor Activity (drug effects)
• Oxazines (pharmacology)
• Parkinson Disease, Secondary (chemically induced, physiopathology)
• Phenanthridines (pharmacology)
• Receptors, Dopamine (drug effects, physiology)
• Receptors, Dopamine D1
• Receptors, Dopamine D2