Allergic conjunctivitis is the most common ocular allergic disease. Although very symptomatic it does not endanger vision, and topical
antihistamines or
chromones are the first choice treatment in clinical practice. Recently, equivalent nanomolar affinities for
histamine H and
muscarinic M 1 and M3 cloned human receptors have been reported for
desloratadine, the active metabolite of
loratadine, a widely prescribed
antihistamine. This property might enhance its utility in the treatment of
asthma, but could induce adverse
anticholinergic effects after
topical administration. In the present study, we compare the
anticholinergic activity of
desloratadine with other known
muscarinic antagonists and
antihistamines on rabbit and guinea-pig iris smooth muscle.
Desloratadine was found to be a competitive antagonist (pA2 = 6.67+/-0.09) of
carbachol-induced contractions in isolated rabbit iris smooth muscle.
Atropine (pA2 = 9.44+/-0.02) and
NPC-14695 (pA2 = 9.18+/-0.03) also behaved as competitive antagonists, whereas
tiotropium bromide (pD'2 = 9.06+/-0.02) exhibited a non-competitive behaviour in this tissue.
Carebastine (pA2 = 5.64+/-0.04) and
fexofenadine (pA2 < 4.0) were also studied. After
topical administration on the guinea-pig eye conjunctiva,
desloratadine produced a potent (ED50 = 2.3 mg/ml) and long lasting
mydriasis (> 120 min at the ED50) in conscious animals.
Fexofenadine and
carebastine were inactive even at the highest concentration tested (10 mg/ml).
Atropine (ED50 = 30 microg/ml) and
tiotropium bromide (ED50 = 10 microg/ml) were much more potent than
desloratadine or
pirenzepine (ED50 = 3 mg/ml) in this model. The competitive
muscarinic antagonism of
desloratadine in vitro, and its potency and duration of action in vivo, suggest that topical treatment of
allergic conjunctivitis and
rhinitis with
desloratadine could produce undesirable peripheral
anticholinergic side effects such as
mydriasis and
xerostomia.