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Goserelin

January 01, 1970

Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer.[1][2] It is an injectable gonadotropin releasing hormone agonist (GnRH agonist).

Goserelin
Clinical data
Trade namesZoladex, others
Other namesD-Ser(But)6Azgly10-GnRH
AHFS/Drugs.comMonograph
MedlinePlusa601002
Pregnancy
category
  • D (3.6mg) / X (10.8mg) (USA)
Routes of
administration		Implant
Drug classGnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding27.3%
Elimination half-life4–5 hours
Identifiers
  • N-(21-((1H-indol-3-yl)methyl)-1,1-diamino-12-(tert-butoxymethyl)-6-(2-(2-carbamoylhydrazinecarbonyl)cyclopentanecarbonyl)-15-(4-hydroxybenzyl)-18-(hydroxymethyl)-25-(1H-imidazol-5-yl)-9-isobutyl-8,11,14,17,20,23-hexaoxo-2,7,10,13,16,19,22-heptaazapentacos-1-en-24-yl)-5-oxopyrrolidine-2-carboxamide
CAS Number
  • 65807-02-5 Y
PubChem CID
  • 5311128
IUPHAR/BPS
  • 3879
DrugBank
  • DB00014 Y
ChemSpider
  • 4470656 Y
UNII
  • 0F65R8P09N
KEGG
  • D04405 Y
ChEBI
  • CHEBI:5523 N
ChEMBL
  • ChEMBL1201247 N
CompTox Dashboard (EPA)
  • DTXSID7048297
ECHA InfoCard100.212.024
Chemical and physical data
FormulaC59H84N18O14
Molar mass1269.433 g·mol−1
3D model (JSmol)
  • Interactive image
  • CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O
  • InChI=1S/C59H84N18O14/c1-31(2)22-40(49(82)68-39(12-8-20-64-57(60)61)56(89)77-21-9-13-46(77)55(88)75-76-58(62)90)69-54(87)45(29-91-59(3,4)5)74-50(83)41(23-32-14-16-35(79)17-15-32)70-53(86)44(28-78)73-51(84)42(24-33-26-65-37-11-7-6-10-36(33)37)71-52(85)43(25-34-27-63-30-66-34)72-48(81)38-18-19-47(80)67-38/h6-7,10-11,14-17,26-27,30-31,38-46,65,78-79H,8-9,12-13,18-25,28-29H2,1-5H3,(H,63,66)(H,67,80)(H,68,82)(H,69,87)(H,70,86)(H,71,85)(H,72,81)(H,73,84)(H,74,83)(H,75,88)(H4,60,61,64)(H3,62,76,90)/t38-,39-,40-,41-,42-,43-,44-,45+,46-/m0/s1 Y
  • Key:BLCLNMBMMGCOAS-URPVMXJPSA-N Y
 NY (what is this?)  (verify)

Structurally, it is a decapeptide. It is the natural GnRH decapeptide with two substitutions to inhibit rapid degradation.

Goserelin stimulates the production of the sex hormones testosterone and estrogen in a non-pulsatile (non-physiological) manner. This causes the disruption of the endogenous hormonal feedback systems, resulting in the down-regulation of testosterone and estrogen production.

It was patented in 1976 and approved for medical use in 1987.[3] It is on the World Health Organization's List of Essential Medicines.[4]

Medical uses edit

 
10.8mg implant syringe

Goserelin is used to treat hormone-sensitive cancers of the breast (in pre- and peri-menopausal women) and prostate, and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty. It may also be used in the treatment of male-to-female transgender people[5] and is favoured above other anti-androgens in some countries, such as the UK. It is available as a 1-month depot and a long-acting 3-month depot.

Goserelin is administered by subcutaneous injection as a biodegradable implant every 28 days for the duration of treatment.[6]

Side effects edit

Goserelin may cause a temporary increase in bone pain and symptoms of prostatic cancer during the first few weeks of treatment. This is known as the tumour flare effect, and is the result of an initial increase in luteinizing hormone production, before the receptors are desensitised and hormonal production is inhibited. The symptoms will disappear, with hormonal inhibition. It is therefore advisable to co-treat with an antiandrogen during the first 2–3 weeks of goserelin treatment, particularly in patients with pre-existing bone symptoms.[citation needed]

Goserelin may cause bone pain, hot flushes, headache, stomach upset, depression, difficulty urinating (isolated cases), weight gain, swelling and tenderness of breasts (infrequent), decreased erections and reduced sexual desire. Bone pain can be managed symptomatically, and erectile dysfunction can be treated by vardenafil (Levitra) or other similar oral therapies, although they will not treat the reduced sexual desire. The rates of gynecomastia with goserelin have been found to range from 1 to 5%.[7]

Short-term memory impairment has also been reported in women and may in some cases be severe, but this effect disappears gradually once treatment is discontinued.[8]<[9]

Pharmacology edit

Goserelin is a synthetic analogue of a naturally occurring gonadotropin-releasing hormone (GnRH). Bioavailability is almost complete by injection. Goserelin is poorly protein-bound and has a serum elimination half-life of two to four hours in patients with normal renal function. The half-life increases with patients with impaired renal function. There is no significant change in pharmacokinetics in subjects with liver failure. After administration, peak serum concentrations are reached in about two hours. It rapidly binds to the GnRH receptor cells in the pituitary gland thus leading to an initial increase in production of luteinizing hormone and thus leading to an initial increase in the production of corresponding sex hormones. This initial flare may be treated by co-prescribing/co-administering an androgen receptor antagonist such as bicalutamide (Casodex). Eventually, after a period of about 14–21 days, production of LH is greatly reduced due to receptor downregulation, and sex hormones are generally reduced to castrate levels.[10]

Chemistry edit

Goserelin is a GnRH analogue and decapeptide. It is provided as the acetate salt.

Society and culture edit

Generic names edit

Goserelin is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name.

References edit

  1. ^ Dictionary of Organic Compounds. CRC Press. 1996. pp. 3372–. ISBN 978-0-412-54090-5.
  2. ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 136–. ISBN 978-94-011-4439-1.
  3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN 9783527607495.
  4. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  5. ^ Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 2005;113:586–92.
  6. ^ "Goserelin". NICE (National Institute for Health and Care Excellence). 2016. Retrieved 19 November 2016.[permanent dead link]
  7. ^ Di Lorenzo G, Autorino R, Perdonà S, De Placido S (December 2005). "Management of gynaecomastia in patients with prostate cancer: a systematic review". The Lancet. Oncology. 6 (12): 972–979. doi:10.1016/S1470-2045(05)70464-2. PMID 16321765.
  8. ^ Newton CR, Yuzpe AA, Timmon IS, Slota MD (October 1993). Memory complaints: a side effect of continued exposure to gonadotropin-releasing hormone agonists (GnRHa). Conjoint Annual Meetings of the American Fertility Society and the Canadian Fertility and Andrology Society. Montreal, Canada.
  9. ^ Friedman AJ, Juneau-Norcross M, Rein MS (February 1993). "Adverse effects of leuprolide acetate depot treatment". Fertility and Sterility. 59 (2): 448–50. doi:10.1016/s0015-0282(16)55701-x. PMID 8425646.
  10. ^ Kotake T, Usami M, Akaza H, Koiso K, Homma Y, Kawabe K, et al. (November 1999). "Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group". Japanese Journal of Clinical Oncology. 29 (11): 562–570. doi:10.1093/jjco/29.11.562. PMID 10678560.

External links edit

  • "Goserelin acetate". Drug Information Portal. U.S. National Library of Medicine.

January 01, 1970
goserelin, sold, under, brand, name, zoladex, among, others, medication, which, used, suppress, production, hormones, testosterone, estrogen, particularly, treatment, breast, prostate, cancer, injectable, gonadotropin, releasing, hormone, agonist, gnrh, agonis. Goserelin sold under the brand name Zoladex among others is a medication which is used to suppress production of the sex hormones testosterone and estrogen particularly in the treatment of breast and prostate cancer 1 2 It is an injectable gonadotropin releasing hormone agonist GnRH agonist GoserelinClinical dataTrade namesZoladex othersOther namesD Ser But 6Azgly10 GnRHAHFS Drugs comMonographMedlinePlusa601002PregnancycategoryD 3 6mg X 10 8mg USA Routes ofadministrationImplantDrug classGnRH analogue GnRH agonist AntigonadotropinATC codeL02AE03 WHO Legal statusLegal statusIn general Prescription only Pharmacokinetic dataProtein binding27 3 Elimination half life4 5 hoursIdentifiersIUPAC name N 21 1H indol 3 yl methyl 1 1 diamino 12 tert butoxymethyl 6 2 2 carbamoylhydrazinecarbonyl cyclopentanecarbonyl 15 4 hydroxybenzyl 18 hydroxymethyl 25 1H imidazol 5 yl 9 isobutyl 8 11 14 17 20 23 hexaoxo 2 7 10 13 16 19 22 heptaazapentacos 1 en 24 yl 5 oxopyrrolidine 2 carboxamideCAS Number65807 02 5 YPubChem CID5311128IUPHAR BPS3879DrugBankDB00014 YChemSpider4470656 YUNII0F65R8P09NKEGGD04405 YChEBICHEBI 5523 NChEMBLChEMBL1201247 NCompTox Dashboard EPA DTXSID7048297ECHA InfoCard100 212 024Chemical and physical dataFormulaC 59H 84N 18O 14Molar mass1269 433 g mol 13D model JSmol Interactive imageSMILES CC C C C H NC O C H COC C C C NC O C H Cc1ccc O cc1 NC O C H CO NC O C H Cc1c nH c2ccccc12 NC O C H Cc1cnc nH 1 NC O C H 1CCC O N1 C O N C H CCCN C N N C O N1CCC C H 1C O NNC N OInChI InChI 1S C59H84N18O14 c1 31 2 22 40 49 82 68 39 12 8 20 64 57 60 61 56 89 77 21 9 13 46 77 55 88 75 76 58 62 90 69 54 87 45 29 91 59 3 4 5 74 50 83 41 23 32 14 16 35 79 17 15 32 70 53 86 44 28 78 73 51 84 42 24 33 26 65 37 11 7 6 10 36 33 37 71 52 85 43 25 34 27 63 30 66 34 72 48 81 38 18 19 47 80 67 38 h6 7 10 11 14 17 26 27 30 31 38 46 65 78 79H 8 9 12 13 18 25 28 29H2 1 5H3 H 63 66 H 67 80 H 68 82 H 69 87 H 70 86 H 71 85 H 72 81 H 73 84 H 74 83 H 75 88 H4 60 61 64 H3 62 76 90 t38 39 40 41 42 43 44 45 46 m0 s1 YKey BLCLNMBMMGCOAS URPVMXJPSA N Y N Y what is this verify Structurally it is a decapeptide It is the natural GnRH decapeptide with two substitutions to inhibit rapid degradation Goserelin stimulates the production of the sex hormones testosterone and estrogen in a non pulsatile non physiological manner This causes the disruption of the endogenous hormonal feedback systems resulting in the down regulation of testosterone and estrogen production It was patented in 1976 and approved for medical use in 1987 3 It is on the World Health Organization s List of Essential Medicines 4 Contents 1 Medical uses 2 Side effects 3 Pharmacology 4 Chemistry 5 Society and culture 5 1 Generic names 6 References 7 External linksMedical uses edit nbsp 10 8mg implant syringe Goserelin is used to treat hormone sensitive cancers of the breast in pre and peri menopausal women and prostate and some benign gynaecological disorders endometriosis uterine fibroids and endometrial thinning In addition goserelin is used in assisted reproduction and in the treatment of precocious puberty It may also be used in the treatment of male to female transgender people 5 and is favoured above other anti androgens in some countries such as the UK It is available as a 1 month depot and a long acting 3 month depot Goserelin is administered by subcutaneous injection as a biodegradable implant every 28 days for the duration of treatment 6 Side effects editGoserelin may cause a temporary increase in bone pain and symptoms of prostatic cancer during the first few weeks of treatment This is known as the tumour flare effect and is the result of an initial increase in luteinizing hormone production before the receptors are desensitised and hormonal production is inhibited The symptoms will disappear with hormonal inhibition It is therefore advisable to co treat with an antiandrogen during the first 2 3 weeks of goserelin treatment particularly in patients with pre existing bone symptoms citation needed Goserelin may cause bone pain hot flushes headache stomach upset depression difficulty urinating isolated cases weight gain swelling and tenderness of breasts infrequent decreased erections and reduced sexual desire Bone pain can be managed symptomatically and erectile dysfunction can be treated by vardenafil Levitra or other similar oral therapies although they will not treat the reduced sexual desire The rates of gynecomastia with goserelin have been found to range from 1 to 5 7 Short term memory impairment has also been reported in women and may in some cases be severe but this effect disappears gradually once treatment is discontinued 8 lt 9 Pharmacology editGoserelin is a synthetic analogue of a naturally occurring gonadotropin releasing hormone GnRH Bioavailability is almost complete by injection Goserelin is poorly protein bound and has a serum elimination half life of two to four hours in patients with normal renal function The half life increases with patients with impaired renal function There is no significant change in pharmacokinetics in subjects with liver failure After administration peak serum concentrations are reached in about two hours It rapidly binds to the GnRH receptor cells in the pituitary gland thus leading to an initial increase in production of luteinizing hormone and thus leading to an initial increase in the production of corresponding sex hormones This initial flare may be treated by co prescribing co administering an androgen receptor antagonist such as bicalutamide Casodex Eventually after a period of about 14 21 days production of LH is greatly reduced due to receptor downregulation and sex hormones are generally reduced to castrate levels 10 Chemistry editGoserelin is a GnRH analogue and decapeptide It is provided as the acetate salt Society and culture editGeneric names edit Goserelin is the generic name of the drug and its INNTooltip International Nonproprietary Name USANTooltip United States Adopted Name and BANTooltip British Approved Name References edit Dictionary of Organic Compounds CRC Press 1996 pp 3372 ISBN 978 0 412 54090 5 Morton IK Hall JM 6 December 2012 Concise Dictionary of Pharmacological Agents Properties and Synonyms Springer Science amp Business Media pp 136 ISBN 978 94 011 4439 1 Fischer J Ganellin CR 2006 Analogue based Drug Discovery John Wiley amp Sons p 514 ISBN 9783527607495 World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 Dittrich R Binder H Cupisti S Hoffmann I Beckmann MW Mueller A Endocrine treatment of male to female transsexuals using gonadotropin releasing hormone agonist Exp Clin Endocrinol Diabetes 2005 113 586 92 Goserelin NICE National Institute for Health and Care Excellence 2016 Retrieved 19 November 2016 permanent dead link Di Lorenzo G Autorino R Perdona S De Placido S December 2005 Management of gynaecomastia in patients with prostate cancer a systematic review The Lancet Oncology 6 12 972 979 doi 10 1016 S1470 2045 05 70464 2 PMID 16321765 Newton CR Yuzpe AA Timmon IS Slota MD October 1993 Memory complaints a side effect of continued exposure to gonadotropin releasing hormone agonists GnRHa Conjoint Annual Meetings of the American Fertility Society and the Canadian Fertility and Andrology Society Montreal Canada Friedman AJ Juneau Norcross M Rein MS February 1993 Adverse effects of leuprolide acetate depot treatment Fertility and Sterility 59 2 448 50 doi 10 1016 s0015 0282 16 55701 x PMID 8425646 Kotake T Usami M Akaza H Koiso K Homma Y Kawabe K et al November 1999 Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer a multicenter randomized controlled trial in Japan Zoladex Study Group Japanese Journal of Clinical Oncology 29 11 562 570 doi 10 1093 jjco 29 11 562 PMID 10678560 External links edit Goserelin acetate Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Goserelin amp oldid 1190942670, wikipedia, wiki, book, books, library,

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