Nasal vasoconstrictor activity of a novel PGE2 analog

A novel PGE2 analog (CL 116,069) was shown to be effective in dogs as a nasal decongestant. Threshold doses were approximately 0.1 microgram/kg with intravenous administration and between 0.08 and 4 microgram with topical administration. CL 116,069 was compared to 17-phenyltrinor PGE2 (CL 116,147), a compound recently studied in humans, and xylometazoline, a well-known nasal decongestant. When given i.v., efficacious doses of xylometazoline tended to raise blood pressure and be shorter acting than the PGs, which did not affect blood pressure. When given topically, all three were long-acting. CL 116,069 usually had the lowest threshold and CL 116,147 usually induced the smallest response. All three agents were more effective than PGE1 or PGE2. A 30-day (b.i.d., topical) toxicity test with CL 116,069 produced no inflammation or nasal pathology and no loss in tissue sensitivity. In vitro examination of xylometazoline and CL 116,069 for vasoconstrictor activity on dog isolated mucosa revealed a response profile similar to that observed with these agents in vivo; i.e., the magnitude of response was comparable for both agents but the t 1/2 was only 74 minutes for xylometazoline and greater than 6.5 hours for CL 116,069. The data suggest that CL 116,069 may provide a therapeutic alternative in which constriction of the nasal blood vessels need not be associated with a generalized vasoconstrictor liability.