A primate model for the evaluation of antihistamines

Area of Science:

• Pharmacology
• Allergy and Immunology
• Otolaryngology

Background:

• Evaluating antihistamine efficacy in human upper airway conditions is challenging due to a lack of objective nasal response measures.
• Developing reliable animal models is crucial for preclinical assessment of drug effectiveness.

Purpose of the Study:

• To establish a rhesus monkey model for objective evaluation of antihistamine effectiveness in upper airway pathology.
• To assess the efficacy of cetirizine using the developed monkey model.

Main Methods:

• Utilized computer-assisted active anterior rhinomanometry to measure nasal airway resistance (NAR) in conscious rhesus monkeys.
• Established antihistamine dose-response relationships by measuring suppression of wheal-and-flare reactions to cetirizine and chlorpheniramine.
• Assessed NAR changes following intranasal histamine provocation, both before and after oral antihistamine pretreatment.

Main Results:

• Oral cetirizine (1.0 mg/kg) and chlorpheniramine (0.2 mg/kg) significantly suppressed histamine-induced wheal-and-flare reactions.
• The monkey model demonstrated reproducible baseline nasal airway resistance measurements.
• Pretreatment with cetirizine (1 mg/kg) or chlorpheniramine (0.2 mg/kg) significantly reduced histamine-induced increases in NAR.

Conclusions:

• The developed rhesus monkey model provides an objective method for evaluating antihistamine efficacy in upper airway conditions.
• Cetirizine demonstrated significant efficacy in reducing histamine-induced nasal airway resistance in this model.