The dopamine D1 agonist SKF 81297 and the dopamine D2 agonist LY 171555 act synergistically to stimulate motor behavior of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned parkinsonian rhesus monkeys

✍ Scribed by R. J. Vermeulen; Dr. B. Drukarch; M. C. R. Sahadat; C. Goosen; E. C. Wolters; J. C. Stoof

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 902 KB
• Volume: 9
• Category: Article
• ISSN: 0885-3185
• DOI: 10.1002/mds.870090613

✦ Synopsis

Abstract

At present, the pharmacotherapy of Parkinson's disease (PD) consists mainly of L‐dihydroxyphenylalanine (L‐DOPA) and/or dopamine D~2~ receptor agonist. However, in general the clinical efficacy of D~2~ agonists is less than that of L‐DOPA. Therefore, attention is being focussed on the role of the D~1~ receptor as a target for therapeutic intervention in PD. Recently, we reported that SKF 81297 is a selective D~1~ agonist that stimulates motor behavior of unilaterally MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine)‐lesioned rhesus monkeys. Presently, we studied the effect of coadministration of SKF 81297 and the D~2~ agonist LY 171555 using the same model of PD. Coadministration of behaviorally active doses of SKF 81297 (0.3 mg/kg) and LY 171555 (0.01 mg/kg) resulted in a prolongation of the motor stimulation induced by either of the drugs alone. Neither administration of SKF 81297, in a dose of 0.03 mg/kg, nor of LY 171555, in a dose of 0.003 mg/kg, were behaviorally active, whereas the combined administration of these compounds induced a significant stimulation of motor behavior. These data suggest that (a) D~1~ receptor stimulation will prove to be useful in the treatment of PD and (b) better therapeutic results will be obtained by simultaneous stimulation of D~1~ and D~2~ receptors as compared with stimulation of both receptors alone.