Penetration of Phenothiazine Derivatives into Dipalmitoyl Lecithin Monolayer

Abstract

Penetration of a series of phenothiazine derivatives (PTZ) dissolved in phosphate buffer (pH 6.92, ionic strength 0.1) into dipalmitoyl lecithin (DPL) monolayer was studied by the measurement of surface pressure (F)-surface area (A) relationships. The surface pressure increase (.DELTA.F) by the penetration of each PTZ into the monolayer under a constant PTZ concentration (10-5 M) at a constant molecular area occupied by DPL (75 .ANG.2/molecule) was assumed to be a characteristic parameter on each PTZ, which represents the difference in hydrophile-lipophile balance and affinity to DPL molecule in liquid-expanded state. Relationships between .DELTA.F and some physico-chemical parameters and pharmacological activities, were examined and discussed from the view point of possibility of employing .DELTA.F as a new physico-chemical parameter which correlates with the pharmacological and clinical potency of psychotropic drugs. The surface pressure increase (.DELTA.F) was found to be correlated with the partition coefficient in n-octanol/water system and also with the surface activity at air-H2O interface and the protein binding capacity. The correlation between .DELTA.F and some pharmacological activities was also confirmed. .DELTA.F was suggested to be a valuable parameter, likewise the partition coefficient in oil/water system, which represents quantitatively the difference in pharmacological potency of a series of phenothiazine derivatives.