TEMPERATURE-DEPENDENCE OF THE BENZODIAZEPINE-RECEPTOR INTERACTION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 22  (1) , 20-25
Abstract
The temperature dependence of the interaction of 3 benzodiazepines with their receptors in rat brain membranes containing .apprx. 2 .mu.M (endogenous) GABA was investigated. van''t Hoff plots of the equilibrium Kd were linear for [3H]diazepam and its N-desmethyl derivative (N-desmethyldiazepam, NDz); for [3H]flunitrazepam a break between 2 linear portions occurred at .apprx. 10.degree. C. Binding of diazepam, NDz and flunitrazepam (for the latter, at temperature > 10.degree. C) is enthalpy-driven (.DELTA.H .apprxeq. -40 to -50 kJ/mol) with a negligible contribution from .DELTA.S. The interaction may not be a simple hydrophobic association, but may be more complex in nature, possibly involving a conformational transition of the receptor-ligand complex. The activation energy for dissociation of the [3H]flunitrazepam- and [3H]diazepam-receptor complexes was .apprx. 100 kJ/mol. The complexes dissociated .apprx. 1000 times faster on changing temperature from 0 to 37.degree. C.