AC-186, a Selective Nonsteroidal Estrogen Receptor beta Agonist, Shows Gender Specific Neuroprotection in a Parkinson's Disease Rat Model

Research output: Contribution to journalArticle


Drugs that selectively activate estrogen receptor beta (ER beta) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ER beta and ER alpha. The selective ER beta 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, 17 beta-estradiol, which activates ER beta and ER alpha 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 ER beta agonist has a differentiated pharmacological profile compared to 17 beta-estradiol in males.


  • Krista McFarland
  • Diana L. Price
  • Christopher N. Davis
  • Jian-Nong Ma
  • Douglas W. Bonhaus
  • Ethan S. Burstein
  • Roger Olsson
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • Parkinson's disease, neuroprotection, AC-186, gender difference, buccal/sublingual administration, selective estrogen receptor beta, agonist
Original languageEnglish
Pages (from-to)1249-1255
JournalACS Chemical Neuroscience
Issue number9
Publication statusPublished - 2013
Publication categoryResearch