Intranasal application of the alpha2-adrenoceptor agonist BHT-920 produces decongestion in the cat.
The effect of alpha2-selective adrenoreceptor activation on nasal cavity dimension in an experimental model of congestion has not been defined. Presently, we used acoustic rhinometry to evaluate the decongestant activity of BHT-920, a selective alpha2-adrenergic agonist against nasal congestion produced by intranasal compound 48/80. Administration of the mast cell liberator compound 48/80 (1%) into a nasal passageway decreased ipsilateral volume and minimum cross-sectional area by 73 +/- 4% and 42 +/- 6%, respectively. The congestant effect of compound 48/80 was blocked by topical BHT-920 (0.3 and 1%) in a dose related manner. In addition, the decrease in minimum cross-sectional area produced by compound 48/80 was attenuated after topical BHT-920 treatment. As a comparison we also evaluated the topical decongestant activity effects of the alpha1-adrenergic agonist phenylephrine, and the nonselective alpha-agonist oxymetazoline. Both phenylephrine (0.1-1.0%) and oxymetazoline (0.01-0.3%) produced decongestion. The blood pressure effects of these three drugs also were evaluated. At doses of 0.3 and 1.0%, BHT-920 did not produce hypertension. In contrast, oxymetaZoline (0.01-0.1%) produced a transient hypertension that peaked at 15 minutes and fully recovered 45 minutes after administration. The hypertensive effect of phenylephrine at 0.3 and 1.0% lasted over 60 minutes. The present findings indicate that selective alpha2-agonists may produce decongestant activity with an improved cardiovascular profile compared with current sympathomimetic drugs such as phenylephrine.
Mcleod
R L
RL
Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Erickson
C H
CH
Mingo
G G
GG
Hey
J A
JA
D000281:Administration, Intranasal; D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001381:Azepines / Q000819:agonists*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009296:Nasal Cavity / Q000187:drug effects; D014663:Nasal Decongestants / Q000819:agonists; D015508:Nasal Obstruction / Q000188:drug therapy; D009299:Nasal Provocation Tests; D010109:Oxymetazoline / Q000819:agonists; D010656:Phenylephrine / Q000819:agonists; D023842:Rhinometry, Acoustic; D013997:Time Factors
D058647:Adrenergic alpha-2 Receptor Agonists; D001381:Azepines; D014663:Nasal Decongestants; D010656:Phenylephrine; C024763:talipexole; D010109:Oxymetazoline