Inhibitory autoreceptor , presynaptic nerve terminal

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Both mianserin and mirtazapine are antidepressant drugs which possess central 0C2 adrenoceptor blocking properties (pA2 7.3). However, mirtazapine is much more potent at histamine Hi receptors (pA2 9.1) and at 5-HT2 and 5-HT3 receptors (pA2 8.2). Blocking of Hi receptors explains the main side effects of mirtazapine, which produces marked sedation and weight gain. Blockade of presynaptic inhibitory 0C2 autoreceptors increases the release of NA, while blockade of presynaptic 0C2 inhibitory heteroreceptors on serotonin nerve terminals (Table 2) is likely to increase the release of serotonin. 

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