Differentiation between two ligands for peripheral benzodiazepine binding sites, [3H]RO5-4864 and [3H]PK 11195, by thermodynamic studies.
The [3H]PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinolinecarboxamide, binding sites in rat cardiac membranes are saturable, with high affinity, specific GABA-independent and correspond to the peripheral type of benzodiazepine. The order of potency of displacing agents was: PK 11195 greater than RO5-4864 greater than dipyridamole greater than diazepam greater than clonazepam. The Bmax obtained with [3H]PK 11195 was equivalent of the Bmax obtained with [3H]RO5-4864 in the same experimental conditions. However thermodynamic analysis indicates that the [3H]PK 11195 binding was entropy driven whereas the [3H]RO5-4864 binding was enthalpy driven. Consequently PK 11195 might be an antagonist of these binding sites and RO5-4864 an agonist or a partial agonist. The simultaneous use of both drugs might help to elucidate the physiological relevance of peripheral benzodiazepine binding sites.
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D002998:Clonazepam / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D004176:Dipyridamole / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013816:Thermodynamics
D001570:Benzodiazepinones; D007546:Isoquinolines; D008024:Ligands; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam; D004176:Dipyridamole; D003975:Diazepam; C037850:PK 11195