TALIPEXOLE OR PRAMIPEXOLE COMBINATIONS WITH CHLORO-APB (SKF-82958) INMPTP-INDUCED HEMIPARKINSONIAN MONKEYS

The effects of two predominant dopamine D-2-like receptor agonists, ta lipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepi ne dihydrochloride, B-HT 920 CL2) and pramipexole ino-4,5,6,7-tetrahyd ro-6-propyl-aminobenzothiazole dihydrochloride, SND 919 CL2Y), were st udied alone and in combination with the selective dopamine D-1-like re ceptor agonist chloro-APB 3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benza zepine hydrobromide, SKF 82958) in five chronic 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) lesioned hemiparkinsonian Macaca nemestr ina monkeys. Talipexole induced contraversive rotation in a dose-depen dent manner up to 32 mu g/kg, i.m. Talipexole was more potent than pra mipexole (10 vs. 32 mu g/kg, i.m.), but pramipexole was mon efficaciou s in producing contraversive rotational behavior and significant hand movements in the afflicted limb. Larger doses of chloro-APB also produ ced contraversive rotation. Combinations of each dopamine D-2-like rec eptor agonist in a median effective dose with chloro-APB (23.4 and 74. 8 mu g/kg, i.m.) had synergistic effects, producing either addition or potentiation, depending upon the dose used. The effects noted with th ese combinations were less than the effect of a large dose (100 mu g/k g) of pramipexole. Talipexole, in the largest dose studied(100 mu g/kg , i.m.), produced sedation which was not seen with the same dose of pr amipexole. No significant extrapyramidal side effects were noted with either agent.