Highlights of clinical studies during the last year are: a) The first 20 subjects in the USA administered intravenous idazoxan, a selective alpha 2 antagonist, tolerated the drug well at doses producing selective and marked increases in the release of norepinephrine following an """"""""orthostatic challenge."""""""" This provides a new tool for testing alpha 2 function. b) In severely depressed patients ECT selectively alters neuropeptide concentrations in cerebrospinal fluid such that endothelin, a probable modifier of signal transduction through several receptors, is markedly increased, neuropeptide Y is elevated and somatostatin is """"""""normalized"""""""" while CRH and neurokinin A are unaffected. c) Platelets and leukocytes from lithium-treated manic-depressives show a significant reduction in the immunolabeling of G alpha q and an increase in pertussis toxin catalyzed [32P] ADP-ribosylation in cultured lymphoblasts from a separate group of bipolars. d) Despite the common classification as benzodiazepine agonists adinazolam and its n-desmethyl metabolite were found to have distinct pharmacodynamic spectrums of activity. Use of pharmacokinetic/pharmacodynamic modelling reveals wide differences in EC30 values for each of several effects - sedation ACTH/cortisol suppression, growth hormone release -suggesting that these are mediated by benzodiazepine receptor complexes with different properties.
