Patanol
Comparative effects of topical ocular anti-allergy drugs on human conjunctival mast cells.

Yanni JM, Miller ST, Gamache DA, Spellman JM, Xu S, Sharif NA.

Ophthalmic Products Research, Alcon Laboratories, Inc., Fort Worth, Texas, USA.

BACKGROUND: The concept of mast cell heterogeneity is well established. Recent data indicate that human conjunctival tissue mast cells and human connective tissue mast cells respond to various secretagogues in similar fashion. It is now recognized that different mast cell populations respond differently to anti-allergic drugs. OBJECTIVE: The purpose of the study is to compare the effects of three new ocular anti-allergic drugs (nedocromil, olopatadine, and pemirolast) on mediator release from the target human conjunctival mast cell population with those of cromolyn sodium. The affinity of the compounds for the histamine H1 receptor was also compared. METHODS: A monodispersed suspension of partially purified human conjunctival mast cells was prepared from cadaver conjunctival tissue. Mast cells (5 x 10(3)) were challenged with anti-human IgE in the presence or absence of test drugs, and histamine content of the cell supernatants was determined using a specific radioimmunoassay. H1 receptor binding activity was assessed using a radioligand binding assay. RESULTS: Cromolyn and pemirolast (100 nM to 1 mM) failed to significantly inhibit histamine release from human conjunctival mast cells using exposure times of 1 and 15 minutes prior to challenge. Using identical nedocromil concentrations and exposure times, statistically significant (P < .05) inhibition (28%) of histamine release was observed at only the 100 microM concentration and 1-minute exposure time. In contrast, olopatadine inhibited histamine release in a concentration-dependent fashion (r = 0.891, n = 59, IC50 = 653 microM). Only olopatadine exhibited significant H1 receptor binding activity at relevant concentrations (Ki = 36 nM, n = 13). CONCLUSIONS: These data indicate that olopatadine possesses anti-allergic activity in the appropriate targets for topical ocular anti-allergic drug therapy, human conjunctival mast cells. Coupled with the compound's antihistaminic activity, this suggests that olopatadine will have efficacy advantages in allergic conjunctivitis patients over the other drugs tested.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9433371&dopt=Abstract olopatadine Patanol



Patanol
Effects of olopatadine hydrochloride on the increase of histamine and peptide-leukotrienes concentrations in nasal lavage fluid following the antigen-antibody reaction in actively sensitized guinea pigs.

Miyake K, Horikoshi K, Ikeda Y, Ishii A, Karasawa A.

Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sizuoka, Japan.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11388650&dopt=Abstract olopatadine Patanol



Patanol
[Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs]

[Article in Japanese]

Iwamoto K, Ikeda J, Nito M, Kosaka N, Ichikawa S, Kobayashi H, Ohmori K.

Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.

Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11436518&dopt=Abstract olopatadine Patanol



Patanol
Inhibitory effect of olopatadine hydrochloride on the sneezing response induced by intranasal capsaicin challenge in guinea pigs.

Kaise T, Akamatsu Y, Ohmori K, Ishii A, Karasawa A.

Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd, Sunto-gun, Shizuoka, Japan. toshihiko.kaise kyowa.co.jp

To investigate the possible inhibitory effect of olopatadine hydrochloride (olopatadine), an antiallergic drug, on the tachykinin-mediated nasal responses, we examined the effect of olopatadine on the sneezing and the nasal rubbing responses induced by intranasal capsaicin challenge in guinea pigs. Olopatadine (10 mg/kg, p.o.) inhibited the sneezing response by 57% without affecting the nasal rubbing one. The antihistamines chlorpheniramine and clemastine did not affect the responses. Morphine caused the inhibition of both responses, which was antagonized by naloxone. These results suggest that olopatadine inhibits the sneezing response by the inhibition of the tachykinin release and not by its antihistaminic action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11459132&dopt=Abstract olopatadine Patanol



Patanol
Effects of olopatadine hydrochloride on the cutaneous vascular hyperpermeability and the scratching behavior induced by poly-L-arginine in rats.

Hayashi K, Kaise T, Ohmori K, Ishii A, Karasawa A.

Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd, Sunto-gun, Shizuoka, Japan.

Intradermal injections of poly-L-arginine induce cutaneous vascular hyperpermeability and scratching behavior in rats. Recently, we elucidated that the plasma extravasation involved both histamine and substance P, while the scratching behavior involved substance P, but not histamine. This study examined the effects of olopatadine hydrochloride (olopatadine), an antiallergic drug with histamine H1-antagonistic action, on the poly-L-arginine-induced responses. Olopatadine (1 mg/kg, p.o.) significantly inhibited both the plasma extravasation and the scratching behavior, suggesting that its inhibitory effects are mediated by the suppression of neuropeptidergic action as well as histaminic action. Olopatadine seems to be a novel-type drug for the treatment of dermatitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11700017&dopt=Abstract olopatadine Patanol