Determination of the membrane-buffer partition coefficient of flunitrazepam, a lipophilic drug.
The partition coefficient (P) of a benzodiazepine, flunitrazepam (FNTZ), was determined in a synaptosomal membrane/buffer system. A two component model was used, one of the components reflecting the drug partitioning into the membrane, and the other the amount of drug in the aqueous phase retained by the pellet after the centrifugation. The quantity of [3H]FTNZ measured as nonspecifically bound to the membrane includes both components so, the second one had to be discounted and in order to determined its magnitude a parallel experiment was performed using a non-partitioning hydrophilic drug (gamma-[3H]aminobutyric acid, [3H]GABA). The assay required previous determination of the fraction of the total volume of the incubation system that corresponded to membrane (fm). The fm value was calculated from the density value (delta) determined by a picnometer method. The results obtained were: delta = 1.66 +/- 0.02; fm = (1.6 +/- 0.2) 10(-3); P = 18.5 +/- 0.8. This P value could explain nonspecific effects of BZDs on some functions of the neuronal membrane.
Perillo
M A
MA
Cátedra de Química Biológica, Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Argentina.
Arce
A
A
D000818:Animals; D002021:Buffers; D002417:Cattle; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D005445:Flunitrazepam / Q000737:chemistry* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013570:Synaptic Membranes / Q000737:chemistry / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002021:Buffers; D008024:Ligands; D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam