Isolation and identification of "diazepam-like" compounds from bovine urine.

Attempts to isolate the putative endogenous ligand for the benzodiazepine receptor from bovine urine resulted in the identification of three isoflavans: equol (1), 3',7-dihydroxyisoflavan (2), and 4'-hydroxy-7-methoxyisoflavan (9), as "diazepam-like" compounds. 3-Chloro-9H-carbazole (17) was found to enhance the binding of diazepam in the benzodiazepine receptor binding assay. Pinosylvine monomethyl ether (18), indigo (20), and indirubin (21) were isolated as inactive compounds.

A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines.

Ex vivo receptor binding as a function of time was determined in Charles River rats. The pharmacokinetic and protein binding parameters in man as well as the ex vivo receptor binding parameters in rat brain for three benzodiazepine induction agents, diazepam, lorazepam and midazolam, were used to develop and test a pharmacokinetic/pharmacodynamic/receptor binding model. The model was subsequently used to predict changes in receptor binding and pharmacodynamics as a function of changes in pharmacokinetics.

Heart norepinephrine levels after exercise training in the rat.

Rats exercise trained by swimming one hour daily five days per week for three months developed cardiac hypertrophy. The NE concentration (0.469 mug/g) and total NE content (0.