The effects of prednisolone, theophylline or salbutamol treatment were studied on leukocyte numbers in bronchoalveolar lavage (BAL) fluid taken 72 h after ovalbumin challenge in sensitized guinea pigs. Ovalbumin challenge resulted in an approximate 3-fold increase in the number of eosinophils in BAL fluid. This increase was significantly reduced by oral administration of prednisolone (59% inhibition with 10mg/ kg × 2) theophylline (56% with 50 mg/kg × 2) but not by salbutamol (10 mg/kg × 2). A comparison with the bronchodilator potency of the above drugs indicated that in guinea pigs salbutamol appears relatively selective as a bronchodilator, prednisolone is selective as an inhibitor of eosinophilia whilst theophylline displays a balance of both activities.

Ebastine (CAS 90729-43-4), cetirizine (CAS 83881-51-0) and loratadine (CAS 79794-75-5) are second generation H1-antihistamines of proven efficacy for treating allergy. Recent clinical studies have found ebastine to be more effective than cetirizine or loratadine in alleviating the symptoms of seasonal allergic rhinitis. The objective of this study was to compare the efficacy of these compounds in three guinea-pig modeles of bronchoconstriction, elicited either by histamine, allergen or leukotriene C4 in order to shed light onto the mechanisms that might explain differences found in clinical studies. In the present experiments, ebastine and cetirizine were equipotent against aerosol histamine-induced bronchospasm in guinea pigs (ED50 115 and 100 micrograms/kg p.o., respectively), while loratadine was three-fold less potent. In the same model the effects of ebastine, loratadine and cetirizine lasted 21, 19 and 15 h, respectively. Ebastine (ED50 334 micrograms/kg p.o.) was the most potent compound in inhibiting allergen-induced bronchospasm in conscious guinea pigs. In vitro studies in tracheally perfused guinea pig lungs demonstrated that ebastine and loratadine inhibited with equal potency the bronchoconstriction induced by leukotriene C4 whilst cetirizine was significantly less potent. Finally, in another in vivo study, ebastine reverted the changes in pulmonary resistance induced by leukotriene C4 in anaesthetised guinea pigs, whereas cetirizine and loratadine were devoid of activity in this model. In accordance with the clinical data, ebastine proved to be the substance with the widest range of application in animal experiments, too.

No abstract

Almotriptan (3-[2-(dimethylamino) ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, CAS 154323-57-6) is a new 5-HT1B/1D agonist whose clinical efficacy has been demonstrated in Phase III clinical trials. This study aimed to evaluate the safety of almotriptan with respect to the central nervous system, renal function and respiratory dynamics using preclinical animal models. The results indicate that almotriptan does not cross the blood-brain barrier, since no effects on/interaction with spontaneous locomotor activity, hexobarbital-induced sleeping time, caffeine-induced increase of spontaneous locomotor activity, or hypothermia (caused by stimulation of central 5-HT1D receptors) was observed following treatment. Almotriptan had a mild antiemetic effect and a slight, transient diuretic effect in dogs, although the latter effect is probably of no clinical relevance. In addition, no effect on the respiratory system of conscious guinea pigs was observed following almotriptan treatment. These results indicate that almotriptan has a favourable safety profile with respect to the central nervous, renal and respiratory systems.

No abstract