A proof of concept trial demonstrating decongestant activity of an alpha2 adrenergic receptor agonist in patients with Seasonal Allergic Rhinitis (SAR)

Pharmacological Characterization of a Novel α2C-Adrenoceptor AgonistN-[3,4-dihydro-4-(1H-imidazol-4-ylmethyl)-2H-1, 4-benzoxazin-6-yl]-N-ethyl-N′-methylurea (Compound A)

“…An ␣ 2 -adrenoceptor agonist, by preferentially constricting venous capacitance blood vessels over arterial resistance blood vessels in nasal mucosa (Corboz et al, 2005(Corboz et al, , 2008, should thus avoid the hypertensive liability of ␣ 1 -adrenoceptor agonists. It is known that ␣ 2 -adrenoceptor agonists produce decongestion in humans, and in the 1960s, the ␣ 2 -adrenoceptor agonist clonidine was initially developed for the treatment of nasal congestion (Stahle, 2000), as was Tinazoline (Nagarajan et al, 1981), and more recently, an ␣ 2 -adrenoceptor agonist demonstrated significant relief of nasal congestion in human subjects with allergic rhinitis (Berkowitz et al, 2005). However, adverse events such as hypotension, bradycardia, somnolence, nausea, and dry mouth, likely caused by activation of the central ␣ 2A -adrenoceptor subtype, were reported.…”