RESUMO
Various 1,4-benzodiazepines were synthesized around a Diazepam, Oxazepam and the n-propyl-1,4-benzodiazepine template. SAR studies of CCK(2) binding affinity were performed and selected examples of each series were tested in vivo in mice. In addition to an anxiolytic effect, antidepressant effects were discovered using 8 standard CNS assays in mice. Finally, the cocomittant administration of the 1,4-benzodiazepine based CCK antagonists enhanced the response to pain with a low dose of morphine, significantly.
RESUMO
The effect of trichloroethylene (TCY) was investigated to determine whether repeated exposure alters the pharmacokinetics of some drugs. Sprague-Dawley rats were given intraperitoneal injections of TCY (5 mmol/kg) in corn oil once daily for 3 days, while the control group received only corn oil. Four hours after the last dose, theophylline, quinidine, or pentobarbital were administered. Blood samples were collected at appropriate intervals for drug analyses. There was a small decrease in plasma clearance of theophylline, with no change in volume of distribution (V(d)) as compared with controls. For quinidine, the elimination half-life was unchanged, and the V(d) was decreased by 40%. The clearance of pentobarbital was decreased by 40% in male rats, but not in the females. Nonetheless, the duration of the sleeping time for both sexes was remarkably prolonged as compared with the control group. There was a decrease in the cytochrome P-450 content only in male rats. In conclusion, exposure to TCY causes changes in some drug kinetics, probably resulting from differential effects on the drug-metabolizing enzymes.