Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo.
Pramipexole (SND 919) is a dopamine D2 autoreceptor agonist which is structurally related to talipexole (B-HT 920), a potential antipsychotic agent. The aim of this study was to investigate the effects of pramipexole on the extracellular concentration of dopamine in vivo. Dopamine and its metabolites, 3,4-dihydrophenylacetic acid and homovanillic acid, were measured in the anterior striatum of freely moving rats by microdialysis and high-performance liquid chromatography with electrochemical detection. Pramipexole (30 and 100 micrograms/kg) caused long-lasting decreases in the extracellular concentrations of dopamine and its metabolites. Talipexole (30 micrograms/kg) produced similar effects. Sulpiride (5 mg/kg), a selective dopamine D2 antagonist, caused a transient increase in the concentration of dopamine and long-lasting increases in the concentrations of its metabolites; it also reversed the effects of pramipexole. SCH-23390 (100 micrograms/kg), a selective dopamine D1 receptor antagonist, caused a transient increase in the concentration of dopamine but did not affect the concentrations of the metabolites. SCH-23390 failed to reverse the effects of pramipexole. These results indicate that pramipexole reduces the extracellular concentrations of dopamine and its metabolites in vivo through a reversible interaction with the dopamine D2 receptor.
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim, F.R.G.
A J
AJ
Carter
R E
RE
Müller
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D052160:Benzothiazoles; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005110:Extracellular Space / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D000077487:Pramipexole; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D001381:Azepines; D052160:Benzothiazoles; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; C024763:talipexole; D013469:Sulpiride; D000077487:Pramipexole; D004298:Dopamine; D006719:Homovanillic Acid