Inhibitory Effect of Olopatadine Hydrochloride on the Sneezing Response Induced by Intranasal Capsaicin Challenge in Guinea Pigs

Kaise, Toshihiko; Akamatsu, Yukino; Ohmori, Kenji; Ishii, Akio; Karasawa, Akira

doi:10.1254/jjp.86.258

Cited by 17 publications

(20 citation statements)

References 13 publications

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“…Since most guinea pigs breath nasally, all the respiratory tract systems from the nasal cavity to the bronchi will be stimulated in inhalation experiments. However, the sneeze reflex is likely to be induced upon nasal cavity stimulation (13), and the cough and sneeze reflexes are generally indistinguishable in inhalation experiments. Therefore, an active expiratory effort with an explosive sound was conventionally counted as a cough in the current experiments.…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Tanaka

Maruyama

2005

J Pharmacol Sci

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Abstract. Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 µM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean ± S.E.M.: 8.85 ± 1.60 and 10.40 ± 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 µl in total in 10 aliquots of 2 µl at 30-s intervals) induced 27.29 ± 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 ± 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg / kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer nonmyelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Aδ-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Aδ-fibers.

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Section: Resultsmentioning

confidence: 99%

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Tanaka

Maruyama

2005

J Pharmacol Sci

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“…Neuropeptide mediators substance P, neurokinin A, nerve growth factor and CGRP have been implicated in the mediation of neurogenic inflammation [26]. Antihistamines may modulate neurogenic inflammation as demonstrated in the animal studies [27]. As a part of the present study, different antihistamines were assessed in the capsaicin-induced rhinitis model.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Anti-Inflammatory Properties and Evidence for No Sedation Liability for the Novel Antihistamine SUN-1334H

Mandhane

Shah

Bahekar

et al. 2009

Int Arch Allergy Immunol

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Background: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called ‘safe’ antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. Method: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. Results: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. Conclusions: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

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“…The mechanism for the capsaicin-induced nasal rubbing response has not fully been elucidated. In this study, morphine at 3 mg/ kg (s.c.) caused significant inhibition of the capsaicin-induced nasal rubbing response, which was antagonized by naloxone (52). Capsaicin not only stimulates the nasal C-fiber afferent nerves to release tachykinins but also transmits the information to the central nervous systems through the trigeminal dorsal horn in the medulla, leading to the sense of pain.…”

Section: -2 Mode Of Action 2-2-1 Histamine H1-receptor Antagonistimentioning

confidence: 98%

“…These results suggest that neuropeptides are involved in allergic obstruction. Kaise et al also investigated the effect of olopatadine on the sneezing and the rubbing responses induced by the intranasal administration of capsaicin in conscious guinea pigs (52), in which the release of tachykinins from sensory nerves are involved (53). Olopatadine at 10 mg/ kg significantly reduced the number of the capsaicin-induced sneezes by 57%, and the drug tended to inhibit the response (Table 1).…”

Section: -2 Mode Of Action 2-2-1 Histamine H1-receptor Antagonistimentioning

confidence: 99%

Pharmacological, Pharmacokinetic and Clinical Properties of Olopatadine Hydrochloride, a New Antiallergic Drug

Ohmori

Hayashi

Kaise

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid monohydrochloride) is a novel antiallergic/ histamine H 1 -receptor antagonistic drug that was synthesized and evaluated in our laboratories. Oral administration of olopatadine at doses of 0.03 mg/ kg or higher inhibited the symptoms of experimental allergic skin responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and rats. Olopatadine is a selective histamine H 1 -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 inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go-related gene channel. Olopatadine was highly and rapidly absorbed in healthy human volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was considerably low in the clearance of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in antiallergic drugs. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritis cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. Ophthalmic solution of olopatadine was also approved in the United States for the treatment of seasonal allergic conjunctivitis in December, 1996 (Appendix: also in the European Union, it was approved in February 2002).

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Inhibitory Effect of Olopatadine Hydrochloride on the Sneezing Response Induced by Intranasal Capsaicin Challenge in Guinea Pigs

Cited by 17 publications

References 13 publications

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Characterization of Anti-Inflammatory Properties and Evidence for No Sedation Liability for the Novel Antihistamine SUN-1334H

Pharmacological, Pharmacokinetic and Clinical Properties of Olopatadine Hydrochloride, a New Antiallergic Drug

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