Receptors and stuff for mol pharm

  1. Estrogen Receptor
    • EL: 17 B-estradiol
    • involved in maintenance of reproductive, cv, musculoskeletal system

    • Ago: Ethinyl estradiol
    • antagonist: tamoxifen, FULVESTERANT (SERD)

    Therapeutics: HRT, Birthcontrol
  2. Androgen receptor
    EL: DHT and testosterone

    Involved in development and maintenance of male reproductive tract and protein anabolism

    • Agonist: methyltestosterone, stanozolol
    • angtagonist: spironolactone

    note: Androstenedione is a common precursor to both testosterone and estrogen, and can lead to gynocomastia
  3. Progesterone Receptor
    EL: Progesterone

    • involved in uterine, reproductive (PR-A)
    • Involved in mammary gland development (PRB)

    • Agonist: medroxyprogesterone, levonorgestrel
    • Antagonist: mifepristone

    Progesteron in BC inhibits the LH surge (thus no ovulation)

    Note: Mifepristone can induce abortion within 50 days (with a 99% success rate),
  4. Glucocorticoid receptor
    EL: cortisol

    increases glucose production in liver, increased fat redistribution,increase muscle breakdown, increase bone loss

    • Agonist: prednisone
    • antagonist:mifepristone (same as progesterone!)
  5. Thyroid Hormone Receptor
    • EL: T3 or T4 (less active)
    • maintain basal metabolic rate; critical for development,especially CNS

    • Agonists: levothyroxine (mixture of T3-T4)
    • Antagonists: none
  6. Vit D Receptor
    EL: calcitriol 

    regulates calcium and phosphorus absorption and homeostasis, bone development, control of cell growth and differentiation

    • Agonists: calcitriol
    • Antagonists: none
  7. Mineralocorticoid Receptor
    EL: aldosterone

    • Sodium reabsorption in distal tubule
    • Note that MR is also activated by cortisol, however kidney expresses 11B-hydroxysteroid dehydrogenase 2, which inactivates cortisol to cortisone [licorice can inactivate this enzyme]

    Agonist: fludrocortisone (treats Addison's disease)

    Antagonists: spironolactone (same as androgen)
  8. Retinoic Acid Receptor
    EL: all trans and 9-cis retinoic acids (ex. Vit A)

    Function: critical for embryonic development,maintenance of usual pigments and maintenance of skin

    • Agonist: istretinoin (accutane)
    • antagonists: none
  9. Retinoid X Receptor
    EL: 9-cis retinoic acid (vit-A)[just like RAR]

    • Agonist: isotretinoin [just like RAR]
    • Antagonists: none

    This is the dimerization partner for Group 1 NRs

    RXR agonists are teratogens!
  10. Peroxisome Proliferator Activated Receptors alpha
    • EL: some fatty acids, eicosanoids, prostanoids
    • Function: promote uptake,utilization and catabolism of fatty acids in liver by upregulating genes involved in fatty acid transport and mitochondrial fatty acid B-oxidation

    Agonists: hypolipidemic agents (fibrate drug class) ex. clofibrate

    Antagonists: none
  11. PPARB
    Cholesterol trafficking in macrophages, promotes formation of Type 1 Muscle fiberds (endurance fibers)

    • Agonists: none
    • Antagonists: none
  12. PPAR-y
    Role in fat cell differentation, including expression of adipocyte specific genes, and promoting formation of mature lipid laden adipocytes

    • Agonists: thiazoladinediones (rosiglitazone)
    • Antagonists: none
  13. Which four receptors work in concert to control hepatic lipid metabolism?
  14. LXR-liver X receptors
    EL: 27-hydroxycholesterol

    controls cholesterol intestinal absorption, catabolism and reverse cholesterol transport from peripheral tissues to liver to bile excretion. 

    No agonists or antagonists
  15. Farnesoid X Receptor
    EL: bile acids

    regulates bile acid homeostasis, decreases bile acid secretion into estine, potential ffor controlling bile acid diarrhea

    • Agonists: obeticholic acid
    • antagonists: guggulsterone
  16. Which two receptor sense endogenous and xenobiotic compounds and enhance elimination?
    PXR and CAR
  17. PXR
    EL: 5b-pregnane-3, 20-dione (very promiscuous receptor)

    Regulates phase 1/2 enzymes, especilaly 3A4 and UGT; regulates P-gp

    • Agonists: hyperforin (St. john's Wart)
    • Antagonists: sulforaphane (cruciferous vegetables)
  18. CAR:
    • EL: no high affinity ligand, but high concentratios of bile acid or bilirubin act as agonists
    • Steroids like androstanes act as inverse agonists

    • Function: regulates phase 1/2 enzymes, especially 3A4 and UGT
    • regulates drug transporter, especially P-GP

    • agonists: phenobarbital (although activation is via phosphorylation, not by binding)
    • Inverse agonists: clotrimazole
    • Antagonists: none
Card Set
Receptors and stuff for mol pharm
Receptors and stuff for mol pharm