title: Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative.
abstract: BACKGROUND
  Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-nor-progesterone, recently completed clinical trials for use with 17beta-estradiol in a new monophasic combined oral contraceptive. In this review, published as well as previously unpublished preclinical studies that detail the effects of NOMAC on estrogenic, progestogenic, and androgenic systems, as well as mineralocorticoid, glucocorticoid, bone, and metabolic indices are described.
  
  
  METHODS
  In vitro assays to determine NOMAC structure-activity relationships used tissue derived from rat uteri. Transactivation profiles were performed using Chinese hamster ovary (CHO) cells transfected with cDNAs encoding human steroid receptors. Estrogenic and anti-estrogenic activities were monitored in vivo in rats as well as in vitro in human breast cancer cells. Standard in vivo techniques were used in rats to determine progestational activity; antigonadotropic, androgenic, mineralocorticoid, and glucocorticoid activities; as well as effects on bone and other metabolic indices. Ovulation inhibition was monitored in rats and primates. NOMAC's effects on cardiovascular systems were determined in dogs and primates.
  
  
  RESULTS
  NOMAC was without significant agonistic or antagonistic activity for estrogen receptor alpha or beta in vitro, and inhibited ovulation in rats and monkeys (2.5 mg/kg and 1 mg/kg, respectively). NOMAC lacked androgenic, antimineralocorticoid, glucocorticoid, and metabolic activity and exhibited moderate anti-androgenic activity in rats. NOMAC did not affect bone mineral density (BMD) in rats or hemodynamic and electrophysiologic parameters in dogs and primates.
  
  
  CONCLUSIONS
  NOMAC is a selective progestogen structurally similar to progesterone that has modest anti-androgenic activity and does not affect lipid or carbohydrate metabolism, BMD, or many cardiovascular parameters in selected animal models.
authors.affiliation: Women's Health Department, Merck Sharp & Dohme Corp,, Oss, The Netherlands. havandiepen@gmail.com
authors.forename: Harry A
authors.initials: HA
authors.lastname: van Diepen
mesh_terms: D000728:Androgens / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016466:CHO Cells; D050260:Carbohydrate Metabolism / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology / Q000633:toxicity; D006224:Cricetinae; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D008535:Megestrol / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009649:Norpregnadienes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010060:Ovulation / Q000187:drug effects; D045167:Progesterone Congeners / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects
chemical_list: D000728:Androgens; D003277:Contraceptives, Oral, Combined; D004967:Estrogens; D009649:Norpregnadienes; D045167:Progesterone Congeners; C038501:nomegestrol acetate; D008535:Megestrol