Azelastine, an orally effective antiasthmatic agent, has been reported to inhibit antihistamine-resistant, leukotriene-mediated allergic bronchoconstriction in guinea pigs. This suggests that azelastine might act through inhibition of leukotriene (LT) C₄/D₄ synthesis. We have examined the effect of azelastine on allergic and nonallergic histamine secretion and LTC₄ formation. Azelastine and the known 5-lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861, exerted concentration-dependent inhibition of allergic LTC₄ formation in chopped lung tissue from actively sensitized guinea pigs and calcium ionophore A23187-stimulated LTC₄ synthesis in mixed peritoneal cells from rats. Azelastine also produced concentration-dependent inhibition of allergic and nonallergic histamine secretion from rat peritoneal mast cells. The ability of azelastine to inhibit allergic and nonallergic histamine secretion and LTC₄ generation may contribute to its mode of action and its therapeutic efficacy.

The ability of azelastine to influence allergic bronchial eosinophil infiltration in guinea pigs was studied. Aeroallergen challenge of actively sensitized guinea pigs produces eosinophil infiltration in bronchoalveolar lavage fluid collected 20–24 h after aeroallergen exposure. Azelastine and methylprednisolone, administered orally 2 h before challenge, inhibited eosinophilic infiltration yielding the ED₅₀s of 1.55 and 4.48 mg/kg, respectively. WEB-2086, a platelet-activating factor antagonist (3 mg/kg), and theophylline, a phosphodiesterase inhibitor (30 mg/kg), also suppressed allergic bronchial infiltration of eosinophils by 44%. The data obtained in this study demonstrate that azelastine exerts direct bronchial anti-inflammatory activity in guinea pigs.

The antiphlogistic activity of meseclazone and its major metabolite, 5-chlorosalicylic acid, have been directly compared to acetylsalicylic acid, phenylbutazone, indomethacin and hydrocortisone in rat paw edema induced by eleven different phlogistic agents. Based on the profile of activity and milligram/kilogram potency displayed by meseclazone, it most closely resembles acetylsalicylic acid and phenylbutazone in its mode of action.

Guinea pigs were sensitized by intraperitoneal injection of ovalbumin, 10 μg mixed with 100 mg Al(OH)₃ in saline. On days 15–30 sensitized guinea pigs were challenged with ovalbumin aerosol (0.5 mg/ml, 30 s, 15 psi) which produced immediate asthmatic responses characterized by dyspnea, convulsions, and some deaths during the first 14 min. Twenty to 24 h later the animals were sacrificed with an overdose of pentobarbital, and lungs, bronchi, and lower trachea were dissected and fixed in 10% neutral buffered formalin. Histopathological examination of randomly coded tissues of the respiratory tract revealed a pulmonary eosinophilic cellular infiltrate in the epithelium/subepithelium of trachea, bronchi, and bronchioles as well as the peribronchial, peribronchiolar, and perivascular areas of the lungs. Oral administration of mepyramine (10 mg/kg) 2 h before aeroallergen challenge provided complete protection against immediate asthmatic responses and prevented deaths during the first 14 min without influencing the late phase associated lung eosinophilic cellular infiltrate. The immediate asthmatic responses were not influenced by methylprednisolone (30 mg/kg) administered orally 24 and 2 h before aeroallergen challenge. Following an additional dose of methylprednisolone 4 h after challenge, there was a significant inhibition of pulmonary eosinophilia (30 mg/kg; -24 h, -2 h, and +4 h). These observations suggest that histamine is the principal mediator of immediate asthma attacks in guinea pigs. Methylprednisolone may be acting by inhibiting the production of eosinophil chemotactic factor of anaphylaxis (platelet-activating factor or leukotriene B4) from the alveolar macrophages, T lymphocytes, and perhaps other cells, thus preventing pulmonary eosinophilia.

Tetrabenazine evoked a biphasic response in rectal temperature of the rat following intraperitoneal administration of 4.4–70.0 mg/kg. The initial hyperthermia was inversely related to the dose while the subsequent hypothermia was dose-dependent. This biphasic effect on temperature was similar to that seen with THC at 0.5 mg/kg, thus adding further evidence of a similarity in the mode of action of the two drugs. In contrast, only hypothermia was evident following chlorpromazine administration.