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.