Abstract
Levocabastine, selected from a series of cyclohexylpiperidine derivatives protects rats from compound 48/80-induced anaphylactic shock for at least 16 h at the oral dose of 0.0015 mg/kg. At the same dose histamine skin reactions and at slightly higher doses passive cutaneous anaphylactic reactions are inhibited. Blockade of passive cutaneous anaphylactic reactions is obtained with levocabastine, despite absence of peripheral serotonin antagonism and any other known non-specific action that may facilitate inhibition of passive anaphylaxis. In dogs allergic reactions are inhibited at oral doses 40 times lower than ketotifen. In guinea-pigs orally and topically administered levocabastine are remarkably effective against allergic conjunctivitis.
Similar content being viewed by others
References
C. J. E. Niemegeers, F. Awouters, J. M. van Nueten, S. de Nollin and P. A. J. Janssen,Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock. Archs. int. Pharmacodyn. Thér.234, 164–176 (1978).
F. Janssens, M. A. C. Janssen, F. Awouters, C. J. E. Niemegeers and G. Vanden Bussche,Chemical development of astemizole-like compounds. Drug Dev. Res.8, 27–36 (1986).
R. A. Stokbroeckx, M. Luyckx, J. Willems, M. Janssen, J. Bracke, R. Joosen and J. Van Wauwe,Levocabastine (R 50 547): the protype of a chemical series of compounds with specific H 1-antihistaminic activity. Drug. Dev. Res.8, 87–93 (1986).
F. Awouters, J. Vermeire, F. Smeyers, P. Vermote, R. van Beek and C. J. E. Niemegeers,Oral antiallergic activity in Ascaris hypersensitive dogs: A study of known antihistamines and of the new compounds ramastine (R 57 959) and levocabastine (R 50 547). Drug. Dev. Res.8, 95–102 (1986).
J. E. Leysen and W. Gommeren,Drug receptor dissociation time, new tool for drug research: receptor binding affinity and drug-receptor dissociation profiles of serotonin-S 2,dopamine-D 2,histamine-H 1 antagonists, and opiates. Drug. Dev. Res.8, 119–131 (1986).
J. P. van Wauwe,Animal pharmacology of levocabastine: a new type of H 1-antihistamine well suited for topical application. InRhinoconjunctivitis, new perspectives in topical treatment. pp. 27–34 (Eds. N. Mygind and R. M. Naclerio). Hogrefe and Huber Publ., Toronto 1989.
D. J. Finney,Probit analysis. Cambridge University Press (1962).
F. Awouters, C. J. E. Niemegeers and P. A. J. Janssen,Interaction of astemizole and other drugs with PCA, histamine, serotonin and compound 48/80-induced skin reactions in the rat. A procedure to determine anti-allergic effectiveness. Drug. Dev. Res.5, 137–145 (1985).
P. A. J. Janssen, C. J. E. Niemegeers, F. Awouters, K. H. L. Schellekens, A. A. H. P. Megens and T. F. Meert,Pharmacology of risperidone (R 64 766), a new antipsychotic with serotonin-S 2 and dopamine D 2-antagonistic properties. J. Pharmac. Exp. Ther.244, 685–693 (1988).
J. Monbaliu, M. Michiels, R. Woestenborghs, I. Geuens, R. Gasparini and J. Heykants,Pharmacokinetics of levocabastine (R 50 547) in the dog. Naunyn-Schmiedebergs Arch. Pharmacol.330 (Suppl.), R15 (1985).
F. Awouters, C. J. E. Niemegeers and P. A. J. Janssen,Inhibitors of mast cell-mediated shock in the rat: relationship to histamine and serotonin antagonism. Drug. Dev. Res.1, 107–114 (1981).
B. Björksten and N.-I. Max Kjiellman,Double-blind studies with levocabastine, sodium cromoglycate, and placebo in the topical treatment of children with allergic conjunctivitis. InRhinoconjunctivitis, new perspectives in topical treatment. pp. 49–52 (Eds. N. Mygind and R. M. Naclerio). Hogrefe and Huber Publ., Toronto 1989.
K. Holmberg, U. Pipkorn, B. Bake and L.-O. Blychert,Effects of topical treatment with H 1 and H 2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis. Allergy44, 281–287 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Awouters, F., Niemegeers, C.J.E., Jansen, T. et al. Levocabastine: Pharmacological profile of a highly effective inhibitor of allergic reactions. Agents and Actions 35, 12–18 (1992). https://doi.org/10.1007/BF01990945
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01990945