RESUMO
Drugs that selectively activate estrogen receptor ß (ERß) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERß and ERα. The selective ERß agonist AC-186 was evaluated in a rat model of Parkinson's disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17ß-estradiol, which activates ERß and ERα with equal potency, did not show the same neuroprotective benefits as AC-186. Hence, in addition to a beneficial safety profile for use in both males and females, a selective ERß agonist has a differentiated pharmacological profile compared to 17ß-estradiol in males.