Gonadorelin

Gonadorelin
Clinical data
Trade names	Factrel, HRF, Kryptocur, Lutrelef, Lutrepulse, Relefact, others
Other names	Abbott 41070; AY-24031; Hoe-471; RU-19847
Routes of; administration	intravenous, subcutaneous
Drug class	GnRH analogue; GnRH agonist; Progonadotropin
ATC code	H01CA01 (WHO) ; V04CM01 (WHO); QH01CA01 (WHO); QV04CM01 (WHO);
Legal status
Legal status	CA: ℞-only;
Pharmacokinetic data
Metabolism	Hydrolysis
Elimination half-life	10–40 minutes
Identifiers
	IUPAC name (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide;
CAS Number	33515-09-2 ; 71447-49-9 (diacetate); 51952-41-1 (hydrochloride);
PubChem CID	638793;
DrugBank	DB00644;
ChemSpider	33562;
UNII	9O7312W37G;
KEGG	C07607;
ChEBI	CHEBI:5520;
ChEMBL	ChEMBL1007;
CompTox Dashboard (EPA)	DTXSID20873490 ;
ECHA InfoCard	100.046.852
Chemical and physical data
Formula	C55H75N17O13
Molar mass	1182.311 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N)NC(=O)CNC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)NC(=O)[C@H](CC5=CN=CN5)NC(=O)[C@@H]6CCC(=O)N6;
	InChI InChI=1S/C55H75N17O13/c1-29(2)19-38(49(80)67-37(9-5-17-60-55(57)58)54(85)72-18-6-10-43(72)53(84)62-25-44(56)75)66-46(77)26-63-47(78)39(20-30-11-13-33(74)14-12-30)68-52(83)42(27-73)71-50(81)40(21-31-23-61-35-8-4-3-7-34(31)35)69-51(82)41(22-32-24-59-28-64-32)70-48(79)36-15-16-45(76)65-36/h3-4,7-8,11-14,23-24,28-29,36-43,61,73-74H,5-6,9-10,15-22,25-27H2,1-2H3,(H2,56,75)(H,59,64)(H,62,84)(H,63,78)(H,65,76)(H,66,77)(H,67,80)(H,68,83)(H,69,82)(H,70,79)(H,71,81)(H4,57,58,60)/t36-,37-,38-,39-,40-,41-,42-,43-/m0/s1; Key:XLXSAKCOAKORKW-AQJXLSMYSA-N;

Gonadorelin is a gonadotropin-releasing hormone agonist (GnRH agonist) which is used in fertility medicine and to treat amenorrhea and hypogonadism.^[2]^[3]^[4]^[5]^[6]^[7] It is also used in veterinary medicine.^[3]^[5] The medication is a form of the endogenous GnRH and is identical to it in chemical structure.^[2]^[3]^[5]^[7] It is given by injection into a blood vessel or fat or as a nasal spray.^[5]^[1]^[7]

Medical uses

Gonadorelin is used as a diagnostic agent to assess pituitary gland function.^[1] It is also used in the treatment of primary hypothalamic amenorrhea, hypogonadotropic hypogonadism (e.g., Kallmann syndrome), delayed puberty, cryptorchidism, and infertility.^[7]^[8]^[1] Unlike other GnRH analogues, it is not used to suppress sex hormone production.^[9]

Available forms

Gonadorelin is available in a portable infusion pump that provides pulsatile subcutaneous administration of the drug.^[7]^[8] The usual dosage delivered is 5 to 20 μg of gonadorelin per pulse every 90 to 120 minutes.^[7]^[8] It is also available in solution form for intravenous or subcutaneous injection and as a nasal spray.^[7]

Pharmacology

Pharmacodynamics

Gonadorelin is an agonist of the GnRH receptor and is used to induce the secretion of the gonadotropins follicle-stimulating hormone and luteinizing hormone from the pituitary gland and to increase sex hormone production by the gonads.^[7]^[8]

Pharmacokinetics

Gonadorelin has a distribution half-life of 2 to 10 minutes and a very short terminal half-life of 10 to 40 minutes.^[1] It is metabolized by hydrolysis into smaller peptide components.^[1]

History

Gonadorelin was available for medical use, under the brand name Factrel, as early as 1978.^[10]

Society and culture

Generic names

Gonadorelin is the generic name of the drug and its INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name, while gonadorelina is its DCITTooltip Denominazione Comune Italiana and gonadoréline is its DCFTooltip Dénomination Commune Française. The diacetate salt is known as gonadorelin acetate and this is its USANTooltip United States Adopted Name, BANMTooltip British Approved Name, and JANTooltip Japanese Accepted Name, while the hydrochloride salt is known as gonadorelin hydrochloride and this is its USANTooltip United States Adopted Name and BANMTooltip British Approved Name.^[2]^[3]^[5]

Brand names

Free alcohol gonadorelin has been marketed under the brand names Cryptocur, Cystoréline, Fertagyl, GnRH Serono, Gonadorelin, HRF, Kryptocur, LH-RH, Luforan, Pulstim, Relefact, Relisorm L, Stimu-LH, and Wyeth-Ayest HRF.^[3]^[5] Gonadorelin diacetate has been marketed under the brand names Kryptocur, LHRH Ferring, Lutamin, Lutrelef, Lutrepulse, Relisorm L, and Relisorm.^[3]^[5] GnRH hydrochloride has been marketed under the brand names Factrel, HRF, and Luforan.^[3]^[5] Additional brand names of gonadorelin and its salts include Acegon, Conceptyl, Cystorelin, Enagon, Equity Oestrus Control, Fertagyl Cattle, Fertiral, Gonabreed, Gonadorelin Interpharm, Gonasyn, Gonavet Veyx, Hypocrine, Improvest, LH RH Tanabe, LHRH Ferring, LH-RH Ferring, LH-RH Tanabe, Oestracton, OvaCyst, Ovsynch, OVsynch, Ovurelin, Ovarelin, and Relefact LH-RH.^[5] The majority of these brand names are for veterinary use.^[3]^[5]

Availability

Gonadorelin is available widely throughout the world for veterinary use, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Australia, New Zealand, Japan, Taiwan, and in many other countries.^[3]^[5]^[11] However, gonadorelin is not available for clinical use in humans in the United States.^[12]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h "Gonadorelin".
^ ^a ^b ^c Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 745–. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 499–. ISBN 978-3-88763-075-1.
^ 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.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "Gonadorelin injectable Uses, Side Effects & Warnings".
^ Shao WM, Bai WJ, Chen YM, Liu L, Wang YJ (August 2014). "[Micropump infusion of gonadorelin in the treatment of hypogonadotropic hypogonadism in patients with pituitary stalk interruption syndrome: cases analysis and literature review]". Beijing da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences (in Chinese). 46 (4): 642–645. PMID 25131486.
^ ^a ^b ^c ^d ^e ^f ^g ^h Köhn FM, Schill WB (17 July 2017). "Hormone Substitution in Male Infertility". In Allahbadia GN, Chawla MM, Das RB, Garcia EV, Gandhi G, Merchant R (eds.). The Art & Science of Assisted Reproductive Techniques (ART). JP Medical Ltd. pp. 731–. ISBN 978-93-86322-82-1.
^ ^a ^b ^c ^d Mokotoff M (2002). "Peptide and Protein Drugs". In Williams DA, Foye WO, Lemke TL (eds.). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 128–. ISBN 978-0-683-30737-5.
^ Goodman LS, Gilman AD (January 1996). Goodman & Gilman's the Pharmacological Basis of Therapeutics. McGraw-Hill, Health Professions Division. p. 1379. ISBN 978-0-07-026266-9.
^ Bain J, Moskowitz JP, Clapp JJ (1978). "LH and FSH response to gonadotropin releasing hormone (GnRH) in normospermic, oligospermic and azoospermic men". Archives of Andrology. 1 (2): 147–152. doi:10.3109/01485017808988331. PMID 367302.
^ Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. pp. 2106–2108. ISBN 978-0-85369-840-1.
^ "Drugs@FDA: FDA-Approved Drugs". FDA.gov. Retrieved 30 December 2021.

[DrugBank-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h "Gonadorelin".

[Elks2014-2] Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 745–. ISBN 978-1-4757-2085-3.

[IndexNominum2000-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 499–. ISBN 978-3-88763-075-1.

[MortonHall2012-4] 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.

[Drugs.com-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "Gonadorelin injectable Uses, Side Effects & Warnings".

[pmid25131486-6] Shao WM, Bai WJ, Chen YM, Liu L, Wang YJ (August 2014). "[Micropump infusion of gonadorelin in the treatment of hypogonadotropic hypogonadism in patients with pituitary stalk interruption syndrome: cases analysis and literature review]". Beijing da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences (in Chinese). 46 (4): 642–645. PMID 25131486.

[AllahbadiaChawla2017-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h Köhn FM, Schill WB (17 July 2017). "Hormone Substitution in Male Infertility". In Allahbadia GN, Chawla MM, Das RB, Garcia EV, Gandhi G, Merchant R (eds.). The Art & Science of Assisted Reproductive Techniques (ART). JP Medical Ltd. pp. 731–. ISBN 978-93-86322-82-1.

[WilliamsFoye2002-8] Mokotoff M (2002). "Peptide and Protein Drugs". In Williams DA, Foye WO, Lemke TL (eds.). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 128–. ISBN 978-0-683-30737-5.

[GoodmanGilman1996-9] Goodman LS, Gilman AD (January 1996). Goodman & Gilman's the Pharmacological Basis of Therapeutics. McGraw-Hill, Health Professions Division. p. 1379. ISBN 978-0-07-026266-9.

[pmid367302-10] Bain J, Moskowitz JP, Clapp JJ (1978). "LH and FSH response to gonadotropin releasing hormone (GnRH) in normospermic, oligospermic and azoospermic men". Archives of Andrology. 1 (2): 147–152. doi:10.3109/01485017808988331. PMID 367302.

[Martindale-11] Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. pp. 2106–2108. ISBN 978-0-85369-840-1.

[12] "Drugs@FDA: FDA-Approved Drugs". FDA.gov. Retrieved 30 December 2021.

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