Partition coefficients of drugs between lipid bilayer vesicles (liposomes) and water provide fundamental information relating to the drug interactions with biomembranes. Especially, information on the drug partitioning helps understanding the pharmacodynamics and pharmacokinetics of drugs, because most of drugs usually partition into cell membrane by passive diffusion. In the quantitative structure-activity relationship (QSAR) studies of drugs, it has been suggested that the partition coefficients obtained for the liposome system are more effective than those obtained for the n-octanol/water system. [1][2][3] Triflupromazine (TFZ) and chlorpromazine (CPZ) are known as major antipsychotropic drugs of the phenothiazine derivatives and exert their action by antagonizing neuronal D 2 receptor in the brain. Recently, CPZ has been shown to hold promise as a pharmacotherapeutic agent for prion-based afflictions.4) We previously reported the partition coefficients (K p s) of some phenothiazine drugs including TFZ and CPZ for phosphatidylcholine (PC) small unilamellar vesicles (SUV) determined by second-derivative spectrophotometry. 5)The derivative method has been recognized to eliminate the effect of background signals 6,7) and usefully applied to the determination of the partition coefficients of drugs between lipid vesicles and water without the troublesome separation procedures [8][9][10] that may disturb the equilibrium states. Using SUV and large unilamellar vesicles (LUV) prepared from PC and cholesterol, the effects of vesicle size and cholesterol content in the bilayer membranes on the K p values of CPZ and TFZ were also studied by the second-derivative spectrophotometry. 11)A recent fluorescence study by Chen et al. provides that the hydrophobic nature of CPZ drives its general association with membranes, while the cationic nature of CPZ promotes its preferential association with phosphatidylserine (PS) in the bilayer membranes.12) Also, Elferink 13) and Dachary-Prigent 14) reported that CPZ bound preferentially to PC liposomes containing PS, compared to PC liposomes.PS is contained abundantly in the brain and nerve cell membranes as compared to the other organs. While phosphatidylethanolamine (PE), an aminophospholipid as PS and the second major phospholipid component after PC, is distributed widely all over the organs in the body and concerned with the membrane fusion and permeability.Therefore, the effects of these aminophospholipids, PS and PE, on the interactions of phenothiazine drugs with phospholipid bilayer vesicles should be investigated quantitatively, since the quantitative evaluation of the difference in the affinity of the drugs for PC, PS and PE will offer important information to understand their distribution and accumulation in the body.In this study we examined the effects of aminophospholipid contents and vesicle size on the partitioning of TFZ and CPZ into the vesicles (SUV and LUV) by using second-derivative spectrophotometry. Experimental Calculation of Molar Partition CoefficientsThe mol...

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This article analyzes key factors affecting transboundary water cooperation in the Brahmaputra River basin at multiple scales. The analysis of multi-track diplomacy reaffirms the potential of actor-inclusive approaches, arguing for a need to go beyond purely focusing on formal legal norms and consider the possibilities of cultural norms of informal processes of cooperation. Various 'windows of opportunity' exist in the current phase of the Brahmaputra basin's development, leading to exploration of a Zone of Possible Effective Cooperation, arising from the effort to scale up multi-track initiatives as well as broader geo-politicaleconomic changes happening across and beyond the basin.

This article analyzes key factors affecting transboundary water cooperation in the Brahmaputra River basin at multiple scales. The analysis of multi-track diplomacy reaffirms the potential of actor-inclusive approaches, arguing for a need to go beyond purely focusing on formal legal norms and consider the possibilities of cultural norms of informal processes of cooperation. Various 'windows of opportunity' exist in the current phase of the Brahmaputra basin's development, leading to exploration of a Zone of Possible Effective Cooperation, arising from the effort to scale up multi-track initiatives as well as broader geo-politicaleconomic changes happening across and beyond the basin.