title: AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.
abstract: Drugs that selectively activate estrogen receptor β (ERβ) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERβ and ERα. The selective ERβ 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, 17β-estradiol, which activates ERβ 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 ERβ agonist has a differentiated pharmacological profile compared to 17β-estradiol in males.
authors.affiliation: ACADIA Pharmaceuticals Inc. , San Diego, California 92121, United States.
authors.forename: Krista
authors.initials: K
authors.lastname: McFarland
authors.forename: Diana L
authors.initials: DL
authors.lastname: Price
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Davis
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Ma
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Bonhaus
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Burstein
authors.forename: Roger
authors.initials: R
authors.lastname: Olsson
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000627:therapeutic use; D047629:Estrogen Receptor beta / Q000819:agonists*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010052:Ovariectomy; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D045442:Rotarod Performance Test; D012737:Sex Factors; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: C587712:AC-186; D003510:Cyclohexanes; D016207:Cytokines; D047629:Estrogen Receptor beta; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010636:Phenols; D004958:Estradiol; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
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