Stereoselective inhibition of the binding of [3H]PK 11195 to peripheral-type benzodiazepine binding sites by a quinolinepropanamide derivative
| Autor: | Nadine Vaucher, Adam Doble, Claude Gueremy, Philippe Bertrand, Marie-Christine Dubroeucq, J. Benavides, Christian Renault, Andre Uzan, Gérard Le Fur, Djamal Allam, Francoise Guilloux |
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| Rok vydání: | 1986 |
| Předmět: |
PK-11195
Stereochemistry In Vitro Techniques Kidney chemistry.chemical_compound In vivo Adrenal Glands medicine Animals IC50 Brain Chemistry Pharmacology Voltage-dependent calcium channel Myocardium Antagonist Rats Inbred Strains Stereoisomerism Isoquinolines Receptors GABA-A Rats chemistry Quinolines Verapamil Female Stereoselectivity Diazepam medicine.drug |
| Zdroj: | European Journal of Pharmacology. 128:269-272 |
| ISSN: | 0014-2999 |
| Popis: | The specific binding of [3H]PK 11195 to the peripheral-type benzodiazepine binding site is inhibited by the 1-enantiomer of N,N-diethyl-α-methyl-2-phenyl-4-quinolinepropanamide ((−)Q1) but not by its d-enantiomer ((+)Q1). (−)Q1 inhibited [3H]PK 11195 binding to several rat tissues with an IC50 of less than 10nM whereas (+)Q1 was at least 500 times less potent. This stereoselectivity was observed in all the tissues tested (brain, heart, kidney and adrenals). The same stereoselectivity was found for the displacement of the binding of [3H]PK 11195 in vivo, where (−)Q1 had an ID50 between 4–15 mg/kg and (+)Q1 was completely inactive at all doses tested (i.e. up to 40 mg/kg). Neither isomer had appreciable affinity for central-type benzodiazepine binding sites ([3H]diazepam) nor for voltage-sensitive calcium channels ([3H]PN 200210 and [3H]verapamil). |
| Databáze: | OpenAIRE |
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