Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand

Int Arch Allergy Immunol. 2014;165(4):255-64. doi: 10.1159/000370068. Epub 2015 Feb 5.


Background: Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet.

Objective: We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation.

Methods: Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge.

Results: nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03).

Conclusion: This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy
  • Asthma / immunology*
  • Basophils / immunology*
  • Cross-Over Studies
  • Dimethylphenylpiperazinium Iodide / administration & dosage
  • Dimethylphenylpiperazinium Iodide / analogs & derivatives*
  • Dimethylphenylpiperazinium Iodide / pharmacology
  • Double-Blind Method
  • Female
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Phosphoric Diester Hydrolases / blood
  • Pyrophosphatases / blood
  • Random Allocation
  • Receptors, Nicotinic / immunology*
  • Young Adult


  • ENPP3 protein, human
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Dimethylphenylpiperazinium Iodide
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases