Efficacy and potency comparisons among aporphine enantiomers: Effects on dopamine neurons in substantia nigra of rat

Extracellular single unit recording studies were carried out on male rats to determine the responses of dopamine neurons of the substantia nigra to intravenous administration of the enantiomers of the aporphine congeners, apomorphine (APO), N-n-propylnorapomorphine (NPA) and 11-hydroxy-N-n-propylnoraporphine (11-OH-NPa). The R-(−)- configuration was found to be the most critical determinant of the efficacy and potency of the agonists. All R-(−)-aporphines were full agonists, able to inhibit completely firing of dopamine cells. The order of potencies, defined by the ID50s, was: (−)NPA, 2.0±0.4 nmol/kg > (−)11-OH-NPa, 4.7±0.7 nmol/kg > (−)APO, 18.0±4.0 nmol/kg. Thus, potency was increased about 9-fold by replacing the 6N methyl of APO with an n-propyl (NPA). Conversely, the 10-hydroxy was not essential for agonist activity (11-OH-NPa) but could increase potency.