Leuprolide
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Leuprolide
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| 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 |
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| Identifiers | |
| CAS number | |
| ATC code | L02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C59H84N16O12 |
| Mol. mass | 1209.4 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | 3 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
X |
| Legal status |
℞ Prescription only |
| Routes | Implant / Injection |
Leuprorelin (INN) or leuprolide acetate (USAN) is a gonadotropin-releasing hormone agonist (GnRH agonist). Proper Sequence: p-Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
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[edit] Mode of action
By causing constant stimulation of the pituitary GnRH receptors, leuprolide initially causes stimulation (flare), but thereafter decreases pituitary secretion (downregulation) of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
[edit] Clinical usage
Like other GnRH agonists, 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]
A 2005 paper suggested it as a treatment for autism,[4] the hypothetical method of action being the now defunct theory that autism is caused by mercury, with the additional assumption that mercury binds irreversibly to testosterone and therefore leuprolide can help cure autism by lowering the testosterone level and thereby the mercury level.[5] 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.[6] 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.[7][8][9]
Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. [10][11]
Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.[12]
[edit] Approvals
- 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.
- 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.
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) 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, leuprorelin is marketed by Wyeth as Prostap SR(one month injection) and Prostap 3 (three month injection).
[edit] References
- ^ 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:. PMID 16176939. http://humrep.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16176939.
- ^ 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:. PMID 16449344. http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=16449344.
- ^ 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:. PMID 15568711. http://www.astm.org/cgi-bin/SoftCart.exe/JOURNALS/FORENSIC/PAGES/JFS2003035.htm?E+mystore.
- ^ 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:. PMID 15780490.
- ^ Allen A (2007-05-28). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. http://www.slate.com/id/2166939/. Retrieved on 2008-01-30.
- ^ "Testosterone regulation". Research Autism. 2007-05-07. http://www.researchautism.net/interventionitem.ikml?id=24. Retrieved on 2007-08-19.
- ^ "John and Jane Doe v. Ortho-Clinical Diagnostics, Inc", US District Court for the Middle District of North Carolina, July 6, 2006
- ^ "Dr. Mark Geier Severely Criticized", Stephen Barrett, M.D., Casewatch.org
- ^ Mills S, Jones T (2009-05-21). "Physician team's crusade shows cracks". Chicago Tribune. http://www.chicagotribune.com/health/chi-autism-lupron-geiers-may21,0,983359.story. Retrieved on 2009-05-21.
- ^ 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:. PMID 16536753.
- ^ 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:. PMID 16362253.
- ^ Doraiswamy PM, Xiong GL. (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opin Pharmacother 7 (1): 1–10. doi:. PMID 16370917.
[edit] External links
- Lupron Injection (package insert from abbott)
- Reforming (purportedly) Non-Punitive Responses to Sexual Offending (journal article discussing use of Lupron as a form of reforming sex offender law)
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