EFFECTS OF AMITRIPTYLINE, MIANSERIN, PHENOXYBENZAMINE AND PROPRANOLOL ON THE RELEASE OF NORADRENALINE IN THE RAT-BRAIN INVIVO

The post synaptic adrenoceptor antagonists, phenoxybenzamine and propranolol, increase the concentration of normetanephrine in the amygdaloid cortex following their acute administration. However, following their chronic administration phenoxybenzamine had no effect, while propranolol decreased the concentrations of this metabolite in the amygdaloid cortex. The chronic effect of propranolol might be attributable to a blockade of pre-synaptic β-receptors. The acute administration of the pre-synaptic α-adrenoceptor agonist clonidine decreases the concentration of normetanephrine in the rat amygdaloid cortex. Conversely, the blockade of pre-synaptic adrenoceptors by yohimbine increases the normetanephrine concentration. The anti-depressants amitriptyline and mianserin also increase normetanephrine concentrations. When given in combination with clonidine, both yohimbine and mianserin antagonise the clonidine induced decrease in normetanephrine concentrations. Evidence suggests that the antagonism of the effect of clonidine is due to the ability of the drugs to block pre-synaptic α-receptors in this brain region. Amitriptyline, which increases normetanephrine concentrations by decreasing the re-uptake of noradrenaline from the synaptic cleft, does not antagonise the effect of clonidine, thereby providing evidence that it does not affect noradrenaline release by acting on pre-synaptic neurotransmitter release mechanisms. © 1979.