Selective estrogen receptor modulators: tissue actions and potential for CNS protection.
Significant physiologic changes occur during menopause. Evidence exists to suggest that estrogen may be neuroprotective under specific conditions. However, there are limitations in the neuroprotection afforded by standard hormone therapy. Accordingly, alternative agents with selected estrogenic effects may hold even greater promise rather than conventional hormone replacement therapy for the prevention and treatment of CNS injury. Recently, a variety of selective estrogen receptor modulators (SERMs) have been developed to retain the favorable and minimize the adverse side effects of estrogens. This review focuses on the CNS and known neuroprotective effects of two specific SERMs, raloxifene and arzoxifene. Recent studies hint that raloxifene and arzoxifene are neuroprotective and may preserve some elements of cognitive function. However, the mechanism of action is not well described and it is unclear if the beneficial effects of SERMs rely on activation of estrogen receptors.
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014599:Uterus / Q000187:drug effects
D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D018696:Neuroprotective Agents; D010880:Piperidines; D017981:Receptors, Neurotransmitter; D013876:Thiophenes; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; C115121:LY 353381