The antagonism of histamine-induced tracheal and bronchial muscle contraction by diphenhydramine: effect of maturation

British Journal of Pharmacology
J S DouglasA Mukhopadhyay


Airway reactivity in spontaneously breathing unanaesthetized female guinea-pigs was significantly reduced as a consequence of maturation. Threshold doses to histamine (% w/v base) were 0.08% +/- .01 and 0.27% +/- .04 in immature (110 g +/- 2; 1 week old) and mature (837 g +/- 29; 4 months old) animals, respectively. The potency of 2-(2-thiazolyl) ethylamine in tracheal tissues from mature animals was significantly less than that in tissues from immature animals (5.06 +/- .03 vs 5.26 +/- .07). There was no change in the potency of this agonist in bronchial tissues (5.0 +/- .09 vs 4.9 +/- .13). Diphenhydramine reduced tissue contractility in tracheal (30% at 0.1 microM; 50% at 3 microM) but not bronchial tissues. The antihistamine in concentrations ranging from 0.1 microM to 3 microM reduced the potency of histamine 2 to 50 fold in both tissues. Schild plots were linear but slopes were significantly less than unity. pA2 values +/- 95% fiducial limits derived from data from tracheal tissues of immature and mature animals using constrained Schild plots (unit slope) were 7.7 (7.6-7.7) and 7.1 (7.0-7.2), respectively (P less than 0.05). pA2 values for diphenhydramine in bronchial tissues using constrained Schild plots were 7.8 (7.7-7...Continue Reading


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