Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.
Olopatadine hydrochloride (olopatadine; KW‐4679), (Z)‐11‐[(3‐dimethylamino)propylidene]‐6,11‐dihydrodibenz[b,e]oxepin‐2‐acetic acid monohydrochloride, is an antiallergic drug with selective and potent histamine H1 receptor antagonist activity. In the present study, we investigated the effect of olopatadine on the release of peptide leukotrienes (P‐LT), potent inflammatory mediators, from human eosinophils. Human eosinophils were purified from venous blood of healthy donors by negative selection using the anti‐CD16 antibody. When human eosinophils were stimu‐ lated with the calcium ionophore A23187 (1 μmol/L), the amount of P‐LT release was approximately 1200 pg/ 105 cells, while thromboxane (TX) B2 release was under the detection limit (< 20 pg/105 cells). Olopatadine inhibited the A23187‐induced P‐LT release from human eosinophils with an IC50 of 4.5 μmol/L. Ketotifen also inhibited this reaction with an IC50 of 39.4 μmol/L. The inhibitory effect of olopatadine on the P‐LT release may contribute to the antiallergic efficacy of this drug.
ABSTRACT-To investigate the mechanism for the amelioration by olopatadine hydrochloride (olopatadine) of allergic rhinitis, we determined its effects on the increase of chemical mediator concentrations in nasal lavage fluid following the intranasal antigen challenge in guinea pigs actively sensitized with DNP-Ascaris. The concentrations of histamine and peptide-leukotrienes increased 10 min after the challenge. Olopatadine at 10 mg/kg (p.o.) significantly prevented the increase of histamine and tended to inhibit the increase of peptide-leukotrienes. The inhibition by olopatadine of the nasal symptoms seems to involve the inhibitory effect on the releases of histamine and, possibly, p-LTs into the nasal cavity.
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