B-HT 920 and B-HT 958: presynaptic effects on electrically evoked 3H-dopamine release from slices of rat nucleus...

The effects of two thiazoloazepine derivatives, B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine) 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-dopamine were studied. Slices from nucleus accumbens of the rat were preincubated with 3H-dopamine and superfused at 23 degrees C or 37 degrees C. Electrical field stimulation was applied using frequencies of 0.5 or 5 Hz. At 37 degrees C/5 Hz, B-HT 920 markedly and dose-dependently (0.01-0.1 mumol/l) reduced the stimulation evoked overflow of tritium. Its dose-response curve was shifted to the right at 23 degrees C/0.5 Hz and 23 degrees C/5 Hz, respectively. A similar result was obtained with the dopamine receptor agonist, apomorphine (1 mumol/l). B-HT 958 (0.1-10 mumol/l) also reduced electrically induced overflow of tritium at 37 degrees C/5 Hz, had no effect at 23 degrees C/0.5 Hz, and facilitated tritium overflow at 23 degrees C/5 Hz. Sulpiride (10 mumol/l) completely prevented the effects of B-HT 920 (1 mumol/l) or B-HT 958 (1 mumol/l) at 37 degrees C/5 Hz, whereas phentolamine (1 mumol/l) had no effect on the actions of the two drugs under these experimental conditions. From the patterns of effects obtained under the different experimental conditions it is concluded that B-HT 920 acts as full agonist at presynaptic dopamine autoreceptors whereas B-HT 958 acts as partial agonist.