Analysis of the effect of (-)-BPAP, a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

Abstract

Endogenous and synthetic enhancer substances enhance in low concentration the impulse propagation mediated release of transmitters from the catecholaminergic and serotonergic neurons in the brain. The purpose of this study was to see whether uptake or MAO inhibition or agonists have similar enhancing prospectives as the enhancer substances. We measured the electrical stimulation induced release of [3H]-norepinephrine or [3H]-dopamine or [3H]-serotonin from the isolated brain stem of rats. (-)-1-Benzofuran-2-yl)-2-propylaminopentane HCl [(-)-BPAP] was used as a prototype of the enhancer compounds. 50 ng/ml (-)-BPAP was the most effective concentration in enhancing the nerve stimulation induced release of [3H]-norepinephrine and [3H]-dopamine, 10 ng/ml (-)-BPAP was highly effective in enhancing the release of [3H]-serotonin. In contrast, 250 ng/ml desmethylimipramine (DMI), a selective inhibitor of the uptake of norepinephrine, did not change significantly the nerve stimulation induced release of [3H]-norepinephrine and 50 ng/ml fluoxetine, a selective inhibitor of the uptake of serotonin, did not change the release of [3H]-serotonin. Neither 250 ng/ml clorgyline, a selective inhibitor of MAO-A, nor 250 ng/ml lazabemide, a selective inhibitor MAO-B, was capable to significantly increase the nerve stimulation induced release of either [3H]-serotonin or [3H]-norepinephrine. The potent dopamine receptor agonists, pergolide and bromocriptine did not change significantly the release of [3H]-dopamine in 50 ng/ml concentration, which is sufficient to stimulate the dopamine receptors. The results prove that stimulation of catecholaminergic and serotonergic neurons in the brain via the enhancing mechanism is clearly different from influencing uptake or MAO.