Effects of amitriptyline, desipramine and mianserin on noradrenergic transmission in the rat isolated right ventricle.

Abstract

The effects of amitriptyline, desipramine and mianserin on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and field stimulation-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effect of these agents on contractions produced by isoprenaline or by field stimulation are reported. Amitriptyline, desipramine (both at greater than or equal to 10(-8) M) and mianserin at greater than or equal to 10(-7) M inhibited the accumulation of radioactivity from [3H]-noradrenaline. The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-noradrenaline, was not altered by amitriptyline, desipramine or mianserin. Rauwolscine, amitriptyline, desipramine and mianserin (all at 10(-6) M) reduced or reversed the decline in outflow of radioactivity evoked by field stimulation at 5 Hz. Desipramine had no additional effects in the presence of cocaine (10(-5) M) and amitriptyline and mianserin had no further effect in the presence of cocaine and rauwolscine. The effect of desipramine probably represents inhibition of neuronal uptake and that of amitriptyline and mianserin blockade of neuronal uptake and prejunctional alpha 2-adrenoreceptors. The rate of beating in the presence of isoprenaline (10(-6) M) was reduced by amitriptyline (10(-7) M), desipramine (10(-6) M) and mianserin (10(-7)--10(-6) M). Higher concentrations of the antidepressants greatly reduced or abolished the rate and force of beating in the presence of isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)