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Anti-inflammatory properties of mizolastine after oral administration on arachidonic acid-induced cutaneous reaction in the rat.
Arzneimittelforschung. 1998 Feb; 48(2):173-8.A

Abstract

The anti-inflammatory effect of mizolastine (CAS 108612-45-9, SL85.0324-00), a new non-sedative histamine H1-receptor antagonist, was assessed in comparison to loratadine, terfenadine and pyrilamine. Intraplantar injection of arachidonic acid (AA) into the rat paw was followed by a rapid and sustained (> or = 4h) inflammatory oedema. Mizolastine (0.1 to 10 mg/ kg p.o.) inhibited in a dose-dependent manner the time course of the AA-induced paw inflammation as from the dose of 0.1 mg/kg p.o. This effect was maintained for at least the 4 h of observation (-44% at 0.3 mg/kg p.o.) suggesting a long lasting action of mizolastine. Although with higher maximal effect, a similar time course of response was observed with dexamethasone at 0.1 mg/kg p.o. In contrast, at anti-histamine, doses, the histamine H1-receptor antagonists terfenadine (1 to 30 mg/kg p.o.), loratadine (10 mg/kg p.o.), and pyrilamine (10 mg/kg p.o.) failed to inhibit significantly the inflammatory action of AA. Moreover, under conditions of H1-receptors blockade (e.g. when co-administered with pyrilamine or loratadine (10 mg/kg p.o.), the inhibition by mizolastine (0.3 mg/kg) of AA-induced inflammation was unchanged. This suggests that the anti-inflammatory effect of mizolastine was unrelated to its histamine H1-receptor antagonist properties. It is proposed that a primary effect on the lipoxygenase pathway may contribute to this action of mizolastine. This is based on the observations that mizolastine inhibits 5-lipoxygenase activity in vitro. Furthermore, a high dose of mizolastine (50 mg/kg) did not affect the inflammatory response to carrageenin which is mediated by the cyclooxygenase pathway. Together, these data indicate that mizolastine is orally effective in this animal model for cutaneous inflammation. Combined with its blockade of histamine H1-receptors, this property may contribute to its possible use in allergic inflammation or other inflammatory states.

Authors+Show Affiliations

Synthélabo Recherche, Rueil-Malmaison France.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9541729

Citation

Pichat, P, et al. "Anti-inflammatory Properties of Mizolastine After Oral Administration On Arachidonic Acid-induced Cutaneous Reaction in the Rat." Arzneimittel-Forschung, vol. 48, no. 2, 1998, pp. 173-8.
Pichat P, Angel I, Arbilla S. Anti-inflammatory properties of mizolastine after oral administration on arachidonic acid-induced cutaneous reaction in the rat. Arzneimittelforschung. 1998;48(2):173-8.
Pichat, P., Angel, I., & Arbilla, S. (1998). Anti-inflammatory properties of mizolastine after oral administration on arachidonic acid-induced cutaneous reaction in the rat. Arzneimittel-Forschung, 48(2), 173-8.
Pichat P, Angel I, Arbilla S. Anti-inflammatory Properties of Mizolastine After Oral Administration On Arachidonic Acid-induced Cutaneous Reaction in the Rat. Arzneimittelforschung. 1998;48(2):173-8. PubMed PMID: 9541729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory properties of mizolastine after oral administration on arachidonic acid-induced cutaneous reaction in the rat. AU - Pichat,P, AU - Angel,I, AU - Arbilla,S, PY - 1998/5/9/pubmed PY - 1998/5/9/medline PY - 1998/5/9/entrez SP - 173 EP - 8 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 48 IS - 2 N2 - The anti-inflammatory effect of mizolastine (CAS 108612-45-9, SL85.0324-00), a new non-sedative histamine H1-receptor antagonist, was assessed in comparison to loratadine, terfenadine and pyrilamine. Intraplantar injection of arachidonic acid (AA) into the rat paw was followed by a rapid and sustained (> or = 4h) inflammatory oedema. Mizolastine (0.1 to 10 mg/ kg p.o.) inhibited in a dose-dependent manner the time course of the AA-induced paw inflammation as from the dose of 0.1 mg/kg p.o. This effect was maintained for at least the 4 h of observation (-44% at 0.3 mg/kg p.o.) suggesting a long lasting action of mizolastine. Although with higher maximal effect, a similar time course of response was observed with dexamethasone at 0.1 mg/kg p.o. In contrast, at anti-histamine, doses, the histamine H1-receptor antagonists terfenadine (1 to 30 mg/kg p.o.), loratadine (10 mg/kg p.o.), and pyrilamine (10 mg/kg p.o.) failed to inhibit significantly the inflammatory action of AA. Moreover, under conditions of H1-receptors blockade (e.g. when co-administered with pyrilamine or loratadine (10 mg/kg p.o.), the inhibition by mizolastine (0.3 mg/kg) of AA-induced inflammation was unchanged. This suggests that the anti-inflammatory effect of mizolastine was unrelated to its histamine H1-receptor antagonist properties. It is proposed that a primary effect on the lipoxygenase pathway may contribute to this action of mizolastine. This is based on the observations that mizolastine inhibits 5-lipoxygenase activity in vitro. Furthermore, a high dose of mizolastine (50 mg/kg) did not affect the inflammatory response to carrageenin which is mediated by the cyclooxygenase pathway. Together, these data indicate that mizolastine is orally effective in this animal model for cutaneous inflammation. Combined with its blockade of histamine H1-receptors, this property may contribute to its possible use in allergic inflammation or other inflammatory states. SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/9541729/Anti_inflammatory_properties_of_mizolastine_after_oral_administration_on_arachidonic_acid_induced_cutaneous_reaction_in_the_rat_ DB - PRIME DP - Unbound Medicine ER -