Disease relevance of levocabastine

• BACKGROUND: Multiple ocular challenges or seasonal trials have demonstrated the efficacy of levocabastine and nedocromil sodium in the treatment of allergic conjunctivitis [1].
• Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05) [2].
• A late allergic reaction was observed by the patient in 6/11 CPTs performed after placebo treatment and 8/11 after levocabastine treatment [3].
• Conjunctival itching (symptom score) and erythema (percent conjunctival surface) were also better controlled by levocabastine than by nedocromil during provocation (p < 0.05) [1].
• However, the results available to date suggest that the topical formulations of levocabastine are a valuable treatment option in patients with allergic rhinitis and/or conjunctivitis [4].

Psychiatry related information on levocabastine

• At high doses, levocabastine caused a decrease in locomotor activity, prolongation of thiopental-induced sleep, depression of acetic acid-induced writhing in mice and inhibition of active avoidance response in rats, but these adverse effects were much less potent than those seen in diphenhydramine, ketotifen and azelastine [5].

High impact information on levocabastine

• It also displaces 125I-labeled neurotensin from the low-affinity levocabastine-sensitive binding sites but at higher concentrations (34.8 +/- 8.3 nM for adult mouse brain and 82.0 +/- 7.4 nM for adult rat brain) [6].
• Structure, functional expression, and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain [7].
• When the receptor is expressed in Xenopus laevis oocytes, the H1 antihistaminic drug levocabastine, like NT and neuromedin N, triggers an inward current [7].
• This activation is sustained (>1 h) and is also produced by the NTS2 agonist levocabastine [8].
• Both the high affinity receptor-1 (NTR1) and the levocabastine-sensitive NTR2 are internalized after neurotensin binding [9].

Chemical compound and disease context of levocabastine

• We conclude that, in this model of allergic conjunctivitis, levocabastine increased the conjunctival tolerance to an allergen [3].
• Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis [10].
• The efficacy of a new antihistamine, levocabastine, in alleviating the ocular allergic reactions induced by both histamine and 48/80 was evaluated in humans [11].
• The efficacy and tolerance of topical administration (one drop in each eye q.i.d.) of levocabastine (0.5 mg/ml) was compared with that of sodium cromoglycate (20 mg/ml) and placebo in a 4-week double-blind trial in patients with seasonal allergic conjunctivitis [12].
• RESULTS: Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05) [13].

Biological context of levocabastine

• Three long-term studies (10-16 weeks' duration) showed absence of tachyphylaxis during prolonged treatment with levocabastine [14].
• Pharmacokinetics of orally administered levocabastine in patients with renal insufficiency [15].
• 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone [16].
• The IC50 for levocabastine was 7 nM [17].
• Influence of levocabastine suspension on ciliary beat frequency and mucociliary clearance [18].

Anatomical context of levocabastine

• The pharmacological properties of this receptor correspond to those of the low-affinity, levocabastine-sensitive NT binding site described initially in membranes prepared from rat and mouse brain [7].
• After a preliminary provocation to determine conjunctival reaction threshold (erythema of at least 50% of the conjunctiva with ocular itching), patients were randomized to receive either topical levocabastine (0.05%) or nedocromil (2%) 15 minutes before provocation [1].
• Nedocromil sodium reduced mast cell function, whereas levocabastine appeared to have primarily antihistaminic actions, although it also reduced the expression of intercellular adhesion molecule 1 [19].
• The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells [20].
• CONCLUSION: Levocabastine exerts anti-allergic activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium [20].

Associations of levocabastine with other chemical compounds

• Visual analogue scale ratings in patients' diaries indicated that at the end of therapy, nasal symptoms were less severe in the levocabastine-treated group than in the sodium cromoglycate-treated (p = 0.03) or placebo-treated group (p = 0.001) [21].
• BACKGROUND: This study was designed to compare the efficacy and tolerability of a new topical (nasal spray and eye drops) H1-receptor antagonist, levocabastine, with that of orally administered terfenadine for the prophylaxis and treatment of seasonal allergic rhinoconjunctivitis [22].
• Potent histamine H1-receptor antagonists (e.g. azelastine and levocabastine) are approved for local treatment and lead to prompt relief of troublesome symptoms [23].
• Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM) [24].
• Leukocytes obtained from allergic volunteers were preincubated for 30 minutes with levocabastine (doses 10(-8) M to 10(-6) M) and thereafter incubated with allergen [25].

Gene context of levocabastine

• Levocabastine-sensitive neurotensin receptor (NTRL) mRNAs were localized by in situ hybridization in adult and developing mouse brain [26].
• BACKGROUND: Levocabastine is a potent histamine H1 receptor antagonist used topically in the treatment of patients with allergic rhinitis [25].
• The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge [27].
• Ibudilast, but not the other commonly used anti-allergic ophthalmic solutions including cromoglycate, ketotifen, tranilast and levocabastine, potently inhibits purified human PDE4A, 4B, 4C and 4D with IC(50) values at 54, 65, 239 and 166 nM, respectively [28].
• With the ever increasing trend towards topical therapy for the treatment of allergic rhinitis and allergic conjunctivitis, levocabastine is a useful addition to the range of drugs currently available [29].

Analytical, diagnostic and therapeutic context of levocabastine

• Visual analog scale ratings from the patients' diaries showed better results for levocabastine [22].
• Thus, topical administration of levocabastine rapid and effective symptom relief with no apparent serious adverse events in patients with allergic rhinitis and/or conjunctivitis [4].
• Furthermore, results from a number of controlled clinical trials have also shown that topical levocabastine is at least as effective as oral terfenadine for the treatment of allergic rhinoconjunctivitis [4].
• Levocabastine eye drops were studied in 21 clinical trials including 1218 patients with allergic conjunctivitis [14].
• Molecular cloning of a levocabastine-sensitive neurotensin binding site [30].

References