Talipexole or pramipexole combinations with chloro-APB (SKF 82958) in MPTP-induced hemiparkinsonian monkeys.
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.
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Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
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Zhang
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Kohno
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Sasa
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D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000633:toxicity; D001381:Azepines / Q000008:administration & dosage* / Q000633:toxicity; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000008:administration & dosage* / Q000633:toxicity; D052160:Benzothiazoles; D015259:Dopamine Agents / Q000633:toxicity; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000633:toxicity; D004347:Drug Interactions; D005260:Female; D020267:MPTP Poisoning; D008254:Macaca nemestrina; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D000077487:Pramipexole; D012890:Sleep / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000633:toxicity
D000978:Antiparkinson Agents; D001381:Azepines; D001552:Benzazepines; D052160:Benzothiazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; D013844:Thiazoles; C024763:talipexole; C071262:SK&F 82958; D000077487:Pramipexole