XXXV The Nasal and Bronchopulmonary Effects of Oxymetazoline and Kb 227

Abstract

In 1959, Aviado, Wnuck and De Beer" compared the effects of 16 sympathomimetic amines on nasal volume and carotid blood flow in the anesthetized dog. On the basis of nasal pressure and of carotid blood flow, the sympathomimetic amines were divided into three groups: 1) a group exemplified by ephedrine which caused a fall in nasal pressure or decongestion equivalent in intensity to that produced by epinephrine, yet the carotid vasoconstriction was more intense, 2) a group exemplified by naphazoline which caused nasal decongestion more intense than vasoconstriction, and 3) a group exemplified by phenylpropylmethylamine which produced both effects but their related intensity varied from animal to animal. This manner of grouping indicates the comparative sensitivity of nasal vessels compared to carotid blood vessels in general. Subsequent to the above report, several imidazolines were introduced as nasal decongestants; however, none of them had been tested on the nasal pressure in the experimental dog. The imidazolines have been tested on the "receptors" associated with the sympathetic innervation to various visceral organs. Two types of adrenergic receptors are recognized: alpha receptors responsible mainly for smooth muscle constriction and beta receptors for relaxation. It has been shown by Mujic and Van Rossum-" that these imidazolines are pure stimulants to the adrenergic alpha receptors in the vascular system of the cat and the intestinal wall of the rabbit. These compounds were demonstrated to be devoid of beta stimulant action.

The Nasal Respiratory Handicap of Expiratory Airflow Disease: The Response to Bronchodilator Aerosols

“…The behaviour of (Ra+ R n) suggests that the phenylephrine aerosol, which decreased both the elevated nasal and lower airways resistances, was equally as potent as isoproterenol, whose effects on the combined resistance mean reflected only the fall in mean Ra. The drop in the two resistances after pheny lephrine, either given alone or combined with isoproterenol, resembles re ductions reported in these indices by A viado and associates in dogs to whom nasal decongestants were given intravenously [26], but the mechan isms are speculative.…”

Chemistry of Alpha- and Beta-Adrenoceptor Agonists and Antagonists

“…This work led to the introduction of two clinically useful drugs, naphazoline (120), an ex-adrenergic stimulant that found use as a nasal decongestant, and tolazoline (6), an ex-adrenergic blocker with antihypertensive properties but which also causes heart stimulation and is now used as a vasodilator. Further synthesis led to the development of other imidazolines as nasal decongestants, such as tetrahydrozoline (123) (HUTCHEON et at, 1955(HUTCHEON et at, , 1958(HUTCHEON et at, , 1964, xylometazoline (124) (MORIMOTO and TANAKA, 1970), and oxymetazoline (121) (HOTOVY et at, 1961;Mu-JIC and VAN ROSSUM, 1965;CARRILLO et at, 1969) and to the antihistamine antazoline (125) and the ex-adrenergic blocker phentolamine (126) (URECH et aI., 1950). (124) (126) MUJIC and VAN ROSSUM (1965) examined a number of2-substituted imidazolines and found them to be specific directly acting ex-stimulants with no p-agonistic properties.…”