Talipexole or pramipexole combinations with chloro-APB (SKF 82958) in MPTP-induced hemiparkinsonian monkeys

Eur J Pharmacol. 1997 May 1;325(2-3):137-44. doi: 10.1016/s0014-2999(97)00129-5.


The effects of two predominant dopamine D2-like receptor agonists, talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine dihydrochloride, B-HT 920 CL2) and pramipexole (S(-)2-amino-4,5,6,7-tetrahydro-6-propyl-aminobenzothiazole dihydrochloride, SND 919 CL2Y), were studied alone and in combination with the selective dopamine D1-like receptor agonist chloro-APB ((+/-)6-chloro-7-8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benz azepine hydrobromide, SKF 82958) in five chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned hemiparkinsonian Macaca nemestrina monkeys. Talipexole induced contraversive rotation in a dose-dependent manner up to 32 microg/kg, i.m. Talipexole was more potent than pramipexole (10 vs. 32 microg/kg, i.m.), but pramipexole was more efficacious in producing contraversive rotational behavior and significant hand movements in the afflicted limb. Larger doses of chloro-APB also produced contraversive rotation. Combinations of each dopamine D2-like receptor agonist in a median effective dose with chloro-APB (23.4 and 74.8 microg/kg, i.m.) had synergistic effects, producing either addition or potentiation, depending upon the dose used. The effects noted with these combinations were less than the effect of a large dose (100 microg/kg) of pramipexole. Talipexole, in the largest dose studied (100 microg/kg, i.m.), produced sedation which was not seen with the same dose of pramipexole. No significant extrapyramidal side effects were noted with either agent.

MeSH terms

  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / toxicity
  • Azepines / administration & dosage*
  • Azepines / toxicity
  • Basal Ganglia Diseases / chemically induced
  • Behavior, Animal / drug effects
  • Benzazepines / administration & dosage*
  • Benzazepines / toxicity
  • Benzothiazoles
  • Dopamine Agents / toxicity
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / toxicity
  • Drug Interactions
  • Female
  • MPTP Poisoning
  • Macaca nemestrina
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Pramipexole
  • Sleep / drug effects
  • Thiazoles / administration & dosage*
  • Thiazoles / toxicity


  • Antiparkinson Agents
  • Azepines
  • Benzazepines
  • Benzothiazoles
  • Dopamine Agents
  • Dopamine Agonists
  • Thiazoles
  • talipexole
  • SK&F 82958
  • Pramipexole