Nafarelin

Nafarelin
Clinical data
Trade namesSynarel, Nasanyl, others
Other namesNafareline; Nafarelin acetate; RS-94991; RS-94991-298; [6-D-(2-naphthyl)alanine]-GnRH
AHFS/Drugs.comMonograph
MedlinePlusa601082
Pregnancy
category
  • X
Routes of
administration		Nasal spray[1][2]
Drug classGnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityINTooltip Intranasal administration: 2.8% (1.2–5.6%)[2]
Protein binding80%[2]
MetabolismPeptidases (not CYP450Tooltip cytochrome P450)[2]
Elimination half-lifeIN: 2.5–3.0 hours[2]
SCTooltip Subcutaneous injection: 86 hours (metabolites)[2]
ExcretionUrine: 44–55%[2]
Feces: 19–44%[2]
Identifiers
  • (2R)-N-[(2R)-5-carbamimidamido-1-[(2S)-2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]-2-[(2R)-2-[(2R)-2-[(2R)-3-hydroxy-2-[(2S)-2-[(2S)-3-(1H-imidazol-4-yl)-2-{[(2R)-5-oxopyrrolidin-2-yl]formamido}propanamido]-3-(1H-indol-3-yl)propanamido]propanamido]-3-(4-hydroxyphenyl)propanamido]-3-(naphthalen-2-yl)propanamido]-4-methylpentanamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.212.186 Edit this at Wikidata
Chemical and physical data
FormulaC66H83N17O13
Molar mass1322.496 g·mol−1
3D model (JSmol)
  • CC(C)C[C@H](NC(=O)[C@@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(N)=O
  • InChI=1S/C66H83N17O13/c1-36(2)25-48(58(89)76-47(13-7-23-71-66(68)69)65(96)83-24-8-14-54(83)64(95)73-33-55(67)86)77-60(91)50(28-38-15-18-39-9-3-4-10-40(39)26-38)78-59(90)49(27-37-16-19-43(85)20-17-37)79-63(94)53(34-84)82-61(92)51(29-41-31-72-45-12-6-5-11-44(41)45)80-62(93)52(30-42-32-70-35-74-42)81-57(88)46-21-22-56(87)75-46/h3-6,9-12,15-20,26,31-32,35-36,46-54,72,84-85H,7-8,13-14,21-25,27-30,33-34H2,1-2H3,(H2,67,86)(H,70,74)(H,73,95)(H,75,87)(H,76,89)(H,77,91)(H,78,90)(H,79,94)(H,80,93)(H,81,88)(H,82,92)(H4,68,69,71)/t46-,47-,48-,49-,50+,51-,52-,53-,54-/m0/s1 checkY
  • Key:RWHUEXWOYVBUCI-ITQXDASVSA-N checkY
  (verify)

Nafarelin, sold under the brand name Synarel among others, is a gonadotropin-releasing hormone agonist (GnRH agonist) medication which is used in the treatment of endometriosis and early puberty.[1][2] It is also used to treat uterine fibroids, to control ovarian stimulation in in vitro fertilization (IVF), and as part of transgender hormone therapy.[3][4][5][6] The medication is used as a nasal spray two to three times per day.[1][2][7]

Side effects of nafarelin are related to sex hormone deprivation and include symptoms of low testosterone levels and low estrogen levels such as hot flashes, sexual dysfunction, vaginal atrophy, and osteoporosis.[2] Nafarelin is a gonadotropin-releasing hormone agonist (GnRH agonist) and works by preventing the production of sex hormones by the gonads.[1][2] It can lower sex hormone levels by 95% in both sexes.[1][2] Nafarelin is a peptide and an analogue of GnRHTooltip gonadotropin-releasing hormone.[8]

Nafarelin was introduced for medical use in 1990.[9][1][10] It is available widely throughout the world, including in North America, Europe, and elsewhere throughout the world.[11][12] The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other being buserelin.[13]

  1. ^ a b c d e f Chrisp P, Goa KL (April 1990). "Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions". Drugs. 39 (4): 523–551. doi:10.2165/00003495-199039040-00005. PMID 2140979.
  2. ^ a b c d e f g h i j k l m "Synarel® (nafarelin acetate) nasal solution" (PDF). Archived (PDF) from the original on 3 January 2020. Retrieved 10 July 2024.
  3. ^ Minaguchi H, Wong JM, Snabes MC (June 2000). "Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature". The Journal of Reproductive Medicine. 45 (6): 481–489. PMID 10900582.
  4. ^ Cite error: The named reference Mutschler2001 was invoked but never defined (see the help page).
  5. ^ Cite error: The named reference pmid27241976 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference pmid23385274 was invoked but never defined (see the help page).
  7. ^ Magon N (October 2011). "Gonadotropin releasing hormone agonists: Expanding vistas". Indian Journal of Endocrinology and Metabolism. 15 (4): 261–267. doi:10.4103/2230-8210.85575. PMC 3193774. PMID 22028996.
  8. ^ Srivastava V (26 June 2017). Peptide-based Drug Discovery: Challenges and New Therapeutics. Royal Society of Chemistry. pp. 182–. ISBN 978-1-78262-732-6.
  9. ^ Cite error: The named reference Drugs@FDA was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference pmid1984190 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference Drugs.com was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).
  13. ^ Önerci TM (17 August 2013). Nasal Physiology and Pathophysiology of Nasal Disorders. Springer Science & Business Media. pp. 208–. ISBN 978-3-642-37250-6. Archived from the original on 13 January 2023. Retrieved 10 July 2024.