Properties of Olopatadine Hydrochloride, a New Antiallergic/Antihistamine Drug

Abstract

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 Improves Dermatitis Score and Inhibits Scratch Behavior in NC/Nga Mice

“…Olopatadine is a histamine H 1 receptor antagonist and has been approved in Japan as an oral drug for the treatment of allergic rhinitis, chronic urticaria, eczema/dermatitis, prurigo, pruritus, psoriasis vulgaris, and erythema multiforme [25]. Worldwide, olopatadine ophthalmic solution, which inhibits the proinflammatory activity of conjunctival mast cells, is an effective therapy for allergic conjunctivitis [26].…”

The Effect of Antihistamines on Seizures Induced by Increasing-Current Electroshocks: Ketotifen, but Not Olopatadine, Promotes the Seizures in Infant Rats

“…12) After the oral administration of 14 C-olopatadine to adult rats, the radioactivity was the highest at 0.5 h in most tissues, including the brain and it thereafter decreased gradually over several hours, although the relative activity in the brain was less than that in the other organs.…”

“…31) For this reason, these compounds have been reported to produce anticholinergic side effects, such as dry mouth and constipation. 31) On the other hand, olopatadine 12) and fexofenadine, 32) which are so-called secondgeneration antihistamines, do not show affinities for most of the neurotransmitter receptors in the brain including the M 1 receptor, but they instead show a selective affinity for the H 1 receptor. Therefore, we could not rule out the possibility that the effects on the seizures depended on differences in the receptor binding profiles among these compounds, although it is unclear at this time as to whether or not there is any relationship between the antagonistic activities with regard to M 1 receptor and the induction of seizures.…”

“…11) Olopatadine hydrochloride (hereafter referred to as olopatadine) is one of the most selective and efficacious antagonists of histamine H 1 receptors. 12) An ophthalmic solution of olopatadine (Patanol ® ) has been approved in the U.S.A., the European Union and Japan for the treatment of seasonal and perennial allergic conjunctivitis. Furthermore, oral administration of the agent (Allelock ® ) was approved in Japan for the treatment of allergic rhinitis, urticaria, and pruritus concomitant with dermatosis in infants and young children, as well as in adults.…”

Olopatadine, a non‐sedating H1 antihistamine, decreases the nocturnal scratching without affecting sleep quality in atopic dermatitis

“…Half of the subjects received the oral antihistamine, olopatadine hydrochloride (OH: Allelock â 5 mg tablet, Kyowa Hakko Kirin, Tokyo, Japan), and the remaining half only placebo prepared in an identical capsule (Appendices S2 and S3). OH is a second-generation non-sedating antihistamine that is used to treat allergic disorders including urticaria, rhinitis and AD in Japan (4,5). Measurement of scratching duration and electroencephalogram recordings was performed on day À2 and À1, and then, the subjects started taking 5 mg of oral OH or placebo twice daily from day 1 to 7.…”