Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors

Abstract

The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.01 (M), 7.80 (D) and 5.64 (E) with the ileum; 8.06 (M), 7.00 (D) and 6.02 (E) with the trachea. The so called non specific component (at high concentrations) was of comparable intensity in the two organs. The pD'2 values were 5.54-5.66 (M), 4.65-4.38 (D) and 3.82-3.55 (E) with ileal and tracheal muscle, respectively. At low concentrations the equi-active dose-ratio for N/D/E (1/16/2300 on the ileum) became 1/12/110 when the trachea was used as the effector. This is surprising since histaminergic receptors of the two preparations are of the same H1-type. It is suggested that only diphenhydramine and eprozinol are really dualistic, and that the non-specific mechanism of activity differs for each drug with that of eprozinol being effective on tracheal muscle.