Purchase this article with an account.
G. Graff, S.T. Miller, J.M. Yanni, M.M. Momsen, H.L. Brockman; Interactions of Olopatadine and Selected Antihistamines with Model and Natural Membranes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3723.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Characterize the in vitro interaction of olopatadine, desloratadine, ketotifen, azelastine and epinastine with model membranes and its consequences on membrane stability. Methods: Model membranes examined consisted of the argon-buffer interface and monomolecular films of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC). Model membrane interactions were detected as changes in surface pressure (π ), or as leakage of 6-carboxyfluorescein, hemoglobin, LDH and histamine from erythrocyte ghosts, intact erythrocytes, human corneal epithelial and conjunctival mast cells, respectively. Results: Measurements at the argon-buffer interface revealed intrinsic surface activity that ranged from highly surface active to weakly surface active (i.e., Kd,S = 0.06 -17.7mM) in the order of: clemastine ≥ desloratadine > azelastine > ketotifen > epinastine. With exception of epinastine, this order of amphipathic behavior was confirmed by estimates of their dissociation constants (Kd,L) for interaction with SOPC which ranged from 0.04 mM to 1.05 mM. Epinastine showed a disproportionately greater increase in surface activity (17-fold) toward SOPC when compared to other agents (1 to 3-fold). A Kd,L value could not be established for olopatadine because of its low affinity for both the argon-buffer interface and SOPC monolayer. Functional consequences of these interactions were associated with a concentration-dependent leakage of 6-carboxyfluorescein from erythrocyte ghosts and hemoglobin from intact erythrocytes. Assessment of the lytic potential of marketed concentrations of ketotifen (0.025%), azelastine (0.05%) and epinastine (0.05%) revealed significant membrane perturbation of human conjunctival mast cells and human corneal epithelial cells as indexed by LDH release. This was in contrast to the marketed concentration of olopatadine (0.1%) which maintained normal mast cell and corneal epithelial cell membrane function as demonstrated by an insignificant release of LDH. Conclusions: The results show that disruption of natural cell membranes by desloratadine, clemastine azelastine, ketotifen and epinastine is the consequence of their surface activity and interaction with the cell membrane. Olopatadine appears to be unique among the agents tested by demonstrating low intrinsic surface activity, thus limiting its interaction with natural membranes.
This PDF is available to Subscribers Only