In screening cooling agents for their actions in the
oral cavity, the molecule FEMA 4557, registered for use in
chewing gum and
hard candy, produced a long-lasting, stinging, and painful cold, like ice chips on the
throat. To further study its properties, FEMA 4557 was formulated as a
topical gel and shown to relieve
skin discomfort without causing any
skin injury or
irritation. FEMA 4557 relieved
inflammation from
flea bites and a bumble bee sting and relieved the
inflammation of
dermatological disorders such as
skin allergy, urticaria, and
thermal injury. The duration of the anti-inflammatory action was for several hours after a
single application. The pharmacological
potency of FEMA 4557 did not correlate to the EC50
potency at the TRPM8
receptor. Surprisingly, when FEMA 4557 was delivered to the inflamed nasal mucosa with a compressor-
nebulizer, it relieved
nasal stuffiness and inhibited
phlegm secretion in subjects with rhinitis, as measured by patient-outcome responses and an objective gravimetric method, respectively. FEMA 4557 was also effective for treating rhinitis when administered in
nose drops or in a rinse. The effective therapeutic amount of FEMA 4557 was about 1 to 5 mg per retained
dose. The conclusion is that FEMA 4557 is a potent non-irritating
suppressor of acute
inflammation in the
nasal cavity and sinuses, a property not previously described for other topical cooling agents. Thus, FEMA 4557 and related analogs may have therapeutic utility for treating
nasal inflammation and
mucus hypersecretion.