The liposome partitioning system for correlating biological activities of imidazolidine derivatives.
The partitioning of 10 imidazolidines in various liposome/buffer systems (logK'm) has been determined and compared to partitioning in the n-octanol/buffer system (logP'). The logK'm, which was generally greater than the logP', increased or decreased upon the addition of dicetylphosphate (DCP) or stearylamine (STA), respectively, to dimyristoylphosphatidylcholine (DMPC) liposomes. Quantitative correlations of alpha 2-adrenergic potencies of imidazolidines have been made by regression analyses with logP', logK'm, binding affinity, and intrinsic activity. Both central and peripheral potencies correlated with logK'm but not with logP'. Multiple regressions yielded improved predictable quantification of these potencies. Thus, the liposomal membrane system shows certain advantages over the n-octanol/buffer system for the prediction of biological activities of the imidazolidines.
Rogers
J A
JA
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Choi
Y W
YW
D020003:1-Octanol; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002021:Buffers; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008081:Liposomes; D000442:Octanols; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D002021:Buffers; D007093:Imidazoles; D008081:Liposomes; D000442:Octanols; D020003:1-Octanol