EFFECTS OF AMITRIPTYLINE, DESIPRAMINE AND MIANSERIN ON NORADRENERGIC TRANSMISSION IN THE RAT ISOLATED RIGHT VENTRICLE

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Abstract
The effects of amitriptyline [A], desipramine [D] and mianserin [M] on the accumulation of radioactivity from [3H]-noradrenaline [norepinephrine, NE], and on the subsequent spontaneous and field stimulation-evoked outfolw of radioactivity were investigated in the rat isolated right ventricle. The effect of these agents on contractions produced by isoprenaline or by field stimulation are reported. A, D (both at .gtoreq. 10-8 M) and M at .gtoreq. 10-7 M inhibited the accumulation of radioactivity from [3H]-NE. The decline in the spontaneous outflow of radioactivity following loading of the tissue with [3H]-NE was not altered by A, D or M. Rauwolscine, A, D and M (all at 10-6 M) reduced or reversed the decline in outflow of radioactivity evoked by field stimulation at 5 Hz. D had no additional effects in the presence of cocaine (10-5 M) and A and M had no further effect in the presence of cocaine and rauwolscine. The effect of D may represent inhibition of neuronal uptake and that of A and M blockade of neuronal uptake and prejunctional .alpha.2-adrenoreceptors. The rate of beating in the presence of isoprenaline (10-6 M) was reduced by A (10-7 M), D (10-6 M) and M (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. The force of contractions evoked by field stimulation at 5 Hz was slightly increased by A, D and M at 10-7 M and reduced by the antidepressants at 10-5 M. Apparently, in the rat isolated right ventricle, the inability of antidepressants to potentiate contractile responses to field stimulation to a great extent as a consequence of blocking neuronal uptake and prejunctional .alpha.-adrenoreceptors is due to a decreased excitability of the postjunctional .beta.-adrenoreceptors.