Antitussive effectsof diphenhydramine on the citric acid cough response

The presentcontrolled crossover study was conducted in twenty healthy volunteerparticipants who utilized the citric acid aerosol-induced cough response bymeans to determine the efficacy of 25 mg of diphenhydramine having theantitussive property.

The entry for thestudy was restricted to only those participants who displayed a consistent andquantitatively defined response to a 5% citric acid challenge. Participantswere primarily dosed with either a placebo vehicle or 25 mg diphenhydramine ina formulation of 10 ml. After the drug ingestion, participants were challengedat 15, 30, 45, 60, 120, and 240 minutes. After three days, participants wereadministered the alternative treatment and rechallenged at the same given timepoints.

During the testtrial, diphenhydramine was effective at the earliest time point evaluated at 15minutes, and it continued to be effective for more than the entire 4-hourduration of the trial period. Regarding the placebo vehicle, the mean coughcounts did not change much from the baseline. Also, the alleged soothing effectof a liquid formulation and the accommodation to the citric acid spray canjustify all the early and steadily significant activity of diphenhydramine insuppressing the cough response. The initial onset of activity ofdiphenhydramine might be because of its local anaesthetic properties. It mightalso specify that the dose of diphenhydramine be essential for effectiveantitussive activity and could be lower than that required dose for effectiveantihistaminic activity. These results might require additional validation indirect comparisons of several doses of diphenhydramine with positive controlsin this model and clinical cough counting models using pathologic coughindices. A 25 mg dose of diphenhydramine seems to be very effective as anantitussive agent in this trial.

Ref: PackmanEW, Ciccone PE, Wilson J, Masurat T. Antitussive effects of diphenhydramine onthe citric acid aerosol-induced cough response in humans. Int J Clin PharmacolTher Toxicol. 1991 Jun;29(6):218-22.