B-HT 920, B-HT 933, and B-HT 958: presynaptic effects on electrically evoked 3H-noradrenaline release from slices of rat brain cortex and hypothalamus.

The effects of the three azepine compounds, B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]azepine), B-HT 933 [2-amino-6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepine; azepexole] and B-HT 958 (2-amino-6-(p-chloro-benzyl)-4H-5,6,7,8-tetrahydrothiazolo[5,4-d]a zepine) on electrically evoked overflow of 3H-noradrenaline were studied. Slices from parietal cortex (Cx) or nucleus anterior hypothalami (nah) were incubated with 3H-noradrenaline, superfused at 23 degrees C or 37 degrees C in the presence of the noradrenaline uptake inhibitor desipramine (3 mumol/l) and field stimulated at frequencies of 0.3 or 3 Hz. At 37 degrees C/0.3 Hz, B-HT 920 and B-HT 933 concentration-dependently decreased the evoked overflow of tritium in both regions studied, whereas B-HT 958 had no effect. In a second set of experiments each drug was tested under three additional experimental conditions, i.e. 37 degrees C/3 Hz, 23 degrees C/0.3 Hz and 23 degrees C/3 Hz. Increasing the stimulation frequency to 3 Hz or lowering the superfusion temperature to 23 degrees C reduced the effects of B-HT 920 (1 mumol/l) and B-HT 933 (10 mumol/l) as compared to the effects at 37 degrees C/0.3 Hz. When tested at 23 degrees C/3 Hz, both drugs did not significantly affect the evoked overflow of tritium in the Cx or the nah. In contrast, B-HT 958 (10 mumol/l), caused a facilitation of evoked overflow in both regions when the higher stimulation frequency or the lower superfusion temperature was used. Its release-enhancing action was most pronounced at 23 degrees C/3 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)