INHIBITION OF DOPAMINE NEURON FIRING BY PRAMIPEXOLE, A DOPAMINE D-3 RECEPTOR-PREFERRING AGONIST, COMPARISON TO OTHER DOPAMINE-RECEPTOR AGONISTS

Pramipexole, an amino-benzathiazole 6,7-tetrahydro-N-6-propyl-2,6-benz othiazolediamine dihydrochloride monohydrate] direct-acting dopamine r eceptor agonist effective in treating Parkinson's disease, bound selec tively and with high affinity to dopamine D2-like receptors, with high est affinity at dopamine D-3 receptors. Ergot dopamine receptor agonis ts (bromocriptine, lisuride, pergolide) bound to both dopamine and non -dopamine receptors. Although all agonists depressed dopamine neuron f iring, only pramipexole and quinpirole completely silenced firing when administered in slowly-accumulating doses. High-dose pergolide, but n or other ergots, completely suppressed firing when given by a prompt b olus i.v. injection, suggesting efficacy limitations may have involved receptor desensitization for pergolide, but not for bromocriptine and lisuride. We conclude that pramipexole differs from ergot dopamine re ceptor agonists currently used in the treatment of Parkinson's disease by virtue of its selectivity for dopamine receptors, its preferential affinity for the dopamine D-3 receptor subtype, and its greater effic acy for stimulating dopamine receptors, as indicated in these electrop hysiology assays.