Noradrenaline Autoreceptors

Noradrenaline (NE) neurons are endowed with autorecep-tors on their cell bodies, where they exert a negative feedback role on firing rate. They are of the a2A subtype as confirmed by genetic cloning experiments. Such autoreceptors are also located on NE terminals throughout the brain, where they inhibit the release of NE. The prototypical agonist of such receptors is clonidine, which is commercialized mainly for the treatment of high blood pressure. Its hypotensive effect would not, however, be exclusively mediated by its action on autoreceptors as a2-adrenoceptors are also located postsynaptically. Yohimbine, among several agents capable of blocking a2-adrenoceptors, is a relatively selective agent used mainly to treat erectile dysfunction. The antidepressant drugs mirtazapine and mianserin antagonize a2-adrenoceptors, leading to enhanced NE release that contributes to their therapeutic actions in major depression. While mirtazapine acts in part by enhancing indirectly the activation of excitatory a:-adrenoceptors located on serotonin (5HT) neurons, mianserin antagonizes aj-adrenoceptors.

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