Leuprorelin

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Leuprolide
Leuprorelin.svg
Leuprorelin ball-and-stick.png
Systematic (IUPAC) name
N-[1-[[1-[[1-[[1-[[1-[[1-[[5-(diaminomethylideneamino)-1-
[2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxo-pentan-2-
yl]carbamoyl]-3-methyl-butyl]carbamoyl]-3-methyl-
butyl]carbamoyl]-2-(4-hydroxyphenyl)ethyl]
carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-(1H-indol-3-
yl)ethyl]carbamoyl]-2-(3H-imidazol-4-yl)ethyl]-5-oxo-
pyrrolidine-2-carboxamide
Clinical data
Trade names Lupron
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a685040
Pregnancy cat. X
Legal status Prescription only
Routes Implant / Injection
Pharmacokinetic data
Half-life 3 hours
Excretion Renal
Identifiers
CAS number 53714-56-0 YesY
ATC code L02AE02
PubChem CID 441410
IUPHAR ligand 1175
DrugBank DB00007
UNII EFY6W0M8TG N
KEGG D08113 YesY
ChEMBL CHEMBL1201199 N
Chemical data
Formula C59H84N16O12 
Mol. mass 1209.4 g/mol
 N (what is this?)  (verify)

Leuprorelin (INN) or leuprolide acetate (USAN) is a GnRH analog. Proper Sequence: Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt (Pyr = L-Pyroglutamyl)

Mode of action[edit]

Leuprolide acts as an agonist at pituitary GnRH receptors. By interrupting the normal pulsatile stimulation of, and thus desensitizing, the GnRH receptors, it indirectly downregulates the secretion of gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels in both sexes.

Clinical use[edit]

An LH-RH (GnRH) analog, leuprolide may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis[1] or uterine fibroids), to treat precocious puberty,[2] and to control ovarian stimulation in In Vitro Fertilization (IVF). It is considered a possible treatment for paraphilias.[3]

Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia.[4][5]

Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.[6]

Leuprolide is also used to treat chronic adrenal disease in ferrets.[citation needed] It also used for treatment of steroid abuse.[citation needed]

Leuprolide, along with triptorelin and goserelin, are often used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy.[7] They are also sometimes used as superior alternatives to anti-androgens like spironolactone and cyproterone acetate for suppressing testosterone production in trans women.

Lupron protocol[edit]

A 2005 paper suggested leuprolide as a possible treatment for autism,[8] the hypothetical method of action being the now defunct hypothesis that autism is caused by mercury, with the additional unfounded assumption that mercury binds irreversibly to testosterone and therefore leuprolide can help cure autism by lowering the testosterone levels and thereby mercury levels.[9] However, used on children or adolescents it could cause disastrous and irreversible damage to sexual functioning, and there is no scientifically valid or reliable research to show its effectiveness in treating autism.[10] This use has been termed the "Lupron protocol"[11] and Mark Geier, the proponent of the hypothesis, has frequently been barred from testifying in vaccine-autism related cases on the grounds of not being sufficiently expert in that particular issue[12][13][14] and has had his medical license revoked.[11] Medical experts have referred to Geier's claims as "junk science".[15]

Approvals[edit]

  • Lupron Injection (5 mg/ml for daily subcutaneous injection) was first approved by the FDA for treatment of advanced prostate cancer on April 9, 1985.
  • Lupron Depot (7.5 mg/vial for monthly intramuscular depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 26, 1989, and subsequently in 22.5 mg/vial and 30 mg/vial for intramuscular depot injection every 3 and 4 months, respectively. 3.75 mg/vial and 11.25 mg/vial dosage forms were subsequently approved for subcutaneous depot injection every month and every 3 months, respectively for treatment of endometriosis or fibroids. 7.5 mg/vial, 11.25 mg/vial, and 15 mg/vial dosage forms were subsequently approved for subcutaneous depot injection for treatment of children with central precocious puberty.
  • Viadur (72 mg yearly subcutaneous implant) was first approved by the FDA for palliative treatment of advanced prostate cancer on March 6, 2000. Bayer will fulfill orders until current supplies are depleted, expected by the end of April 2008
  • Eligard (7.5 mg for monthly subcutaneous depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 24, 2002, and subsequently in 22.5 mg, 30 mg, and 45 mg doses for subcutaneous depot injection every 3, 4, and 6 months, respectively.
  • Leupromer® 7.5 ( 7.5 mg, One month depot for subcutaneous injection) is the second In-situ forming injectable drug in the world. It is used for palliative treatment of advanced prostate cancer, endometriosis and fibroids. It was approved by The Ministry of Health and Medical Education Of Iran.

Leuprolide acetate is marketed by Bayer AG under the brand name Viadur, by Sanofi-Aventis under the brand name Eligard, and by TAP Pharmaceuticals (1985–2008), by Varian Darou Pajooh under the brand name Leupromer and Abbott Laboratories (2008-current) under the brand name Lupron. It is available as a slow-release implant or subcutaneous/intramuscular injection.

In the UK and Ireland, leuprorelin is marketed by Takeda UK as Prostap SR (one-month injection) and Prostap 3 (three-month injection).

See also[edit]

References[edit]

  1. ^ Crosignani PG, Luciano A, Ray A, Bergqvist A (January 2006). "Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain". Human reproduction (Oxford, England) 21 (1): 248–56. doi:10.1093/humrep/dei290. PMID 16176939. 
  2. ^ Badaru A, Wilson DM, Bachrach LK, et al. (May 2006). "Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty". The Journal of Clinical Endocrinology and Metabolism 91 (5): 1862–7. doi:10.1210/jc.2005-1500. PMID 16449344. 
  3. ^ Saleh F, Niel T, Fishman M (2004). "Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series". J Forensic Sci 49 (6): 1343–8. doi:10.1520/JFS2003035. PMID 15568711. 
  4. ^ Schober JM, Byrne PM, Kuhn PJ. (2006). "Leuprolide acetate is a familiar drug that may modify sex-offender behaviour: the urologist's role.". BJU international 97 (4): 684–6. doi:10.1111/j.1464-410X.2006.05975.x. PMID 16536753. 
  5. ^ Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA. (2005). "Leuprolide acetate suppresses pedophilic urges and arousability.". Archives of Sexual Behavior 34 (6): 691–705. doi:10.1007/s10508-005-7929-2. PMID 16362253. 
  6. ^ Doraiswamy PM, Xiong GL. (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opin Pharmacother 7 (1): 1–10. doi:10.1517/14656566.7.1.1. PMID 16370917. 
  7. ^ David A. Wolfe; Eric J. Mash (9 October 2008). Behavioral and Emotional Disorders in Adolescents: Nature, Assessment, and Treatment. Guilford Press. pp. 556–. ISBN 978-1-60623-115-9. Retrieved 24 March 2012. 
  8. ^ Geier M, Geier D (2005). "The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity". Med Hypotheses 64 (5): 946–54. doi:10.1016/j.mehy.2004.11.018. PMID 15780490. 
  9. ^ Allen A (2007-05-28). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. Retrieved 2008-01-30. 
  10. ^ "Testosterone regulation". Research Autism. 2007-05-07. Retrieved 2007-08-19. 
  11. ^ a b "Maryland medical board upholds autism doctor's suspension". Chicago Tribune. May 11, 2011. 
  12. ^ "John and Jane Doe v. Ortho-Clinical Diagnostics, Inc", US District Court for the Middle District of North Carolina, July 6, 2006
  13. ^ "Dr. Mark Geier Severely Criticized", Stephen Barrett, M.D., Casewatch.org
  14. ^ Mills S, Jones T (2009-05-21). "Physician team's crusade shows cracks". Chicago Tribune. Retrieved 2009-05-21. 
  15. ^ 'Miracle drug' called junk science: Powerful castration drug pushed for autistic children, but medical experts denounce unproven claims, Chicago Tribune, May 21, 2009

External links[edit]