Leuprolide

Category: peptide

Aliases: Leuprorelin, Lupron, Eligard, Lupron Depot

Pharmacological Mechanism

Nonapeptide GnRH analog — D-Leu⁶ + Pro⁹-NEt modifications resist degradation, raise receptor affinity ~15× over native GnRH. Initial pulsatile spike flares LH/FSH → testosterone / oestrogen surge in first week (testosterone-flare in prostate cancer); continuous chronic exposure desensitises and down-regulates pituitary GnRH-R → castrate gonadal steroid levels within ~3–4 weeks. Depot microspheres / in-situ-forming gel formulations release drug over 1, 3, 4, or 6 months.

Half-Life (t½)

SC: 3h

Dosing Guidelines

• SC: Typical 5 mg (Range: 3.75–7.5 mg)
• IM: Typical 5 mg (Range: 3.75–7.5 mg)

Target Organ Systems

• nervous
• endocrine
• reproductive

Pathways It Modulates

• GnRH pulse generator (inhibitor) — GnRH-R (continuous agonist → desensitization)

Chemical Identifiers

• PubChem CID: 657181
• Formula: C59H84N16O12
• Molecular weight: 1209.4 g/mol
• InChIKey: GFIJNRVAKGFPGQ-LIJARHBVSA-N
• SMILES: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=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

References

• PMID 12083977