Nafarelin

In plain language

Nafarelin is a GnRH agonist delivered as a nasal spray, sold as Synarel. It is used for endometriosis and for central precocious puberty in children.

It is one of the few peptide drugs that can be sprayed into the nose instead of injected, because a nasal route was workable for its dose and properties. Like other GnRH agonists it suppresses the reproductive hormone axis, which in endometriosis shrinks the hormone-dependent tissue.

For students

Nafarelin is [D-2-Nal6]GnRH (about 1,322 Da), with a bulky naphthylalanine at position 6. It is supplied as a twice-daily nasal spray (200 mcg per spray, one spray per nostril), one of the few commercially successful intranasal peptide products, achieving roughly 2-4% bioavailability.

The nasal route avoids injection-site reactions but introduces local irritation and a strict dose schedule (morning and evening). Indications are endometriosis (pain reduction comparable to danazol with a better safety profile) and central precocious puberty, where it is one of several GnRH agonist options in children.

For researchers and instructors

Biochemistry. The D-2-naphthylalanine substitution at position 6 is more hydrophobic than goserelin's D-Ser(tBu), illustrating how hydrophobic position-6 residues generally increase potency in this class.

Pharmacology. Twice-daily nasal dosing; bioavailability is low but sufficient; the initial flare effect is the same as injectable agonists; add-back therapy with low-dose estrogen is used to mitigate bone loss in long courses.

Human evidence. Randomized comparisons against danazol in endometriosis established comparable pain relief with fewer androgenic side effects; CPP studies support axis suppression in children.

Teaching point. A rare example of a successful intranasal peptide drug, useful for teaching the barriers (bioavailability, mucosal irritation, dose ceiling) to non-injectable peptide delivery.