Noradrenergic synapses

Taiwo YO, Levine JD. (1988). Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. J Neurosci. 8(4) 1346-49. 

FIGURE 2.7 Noradrenergic synapse. The release of norepinephrine (1) can be enhanced by compounds such as amphetamine. Once released, norepinephrine binds to a2 receptors (2a), al receptors (2b), and pi receptors (3). Norepinephrine is removed from the synapse via cleavage by catechol-O-methyl-transferase (COMT) or via reuptake by the norepinephrine transporter (4). 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

Cocaine is a local anesthetic with a peripheral sympathomimetic action that results from inhibition of transmitter reuptake at noradrenergic synapses (see Chapter 6 Introduction to Autonomic Pharmacology). It readily enters the central nervous system and produces an amphetamine-like effect that is shorter lasting and more intense. The major action of cocaine in the central nervous system is to inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain. These properties and the fact that it can be smoked, "snorted" into the nose, or injected for rapid onset of... 

Another important mechanism whereby the release of a neurotransmitter may be altered is by presynaptic inhibition. Initially this mechanism was thought to be restricted to noradrenergic synapses, but it is now known to occur at GABA-ergic, dopaminergic and serotonergic terminals also. 

The presynaptic feedback receptor. In noradrenergic synapses, this is the (x receptor. In dopaminergic... 

Olschowka JA, Molliver ME, Grzanna R, Rice FL, Coyle JT (1981) Ultrastructural demonstration of noradrenergic synapses in the rat central nervous system by dopamine-y8-hydroxylase immunocytochemis-try, J. Histochem. Cytochem., 29, 271-280,... 

Figure 9-10. Pre- and postsynaptic a adrenoceptors of noradrenergic synapses. (From Timmermen and Van Zwieten, 1972). NA = norepinephrine.

The tricyclic antidejn essant drugs imipramine and amitriptyline and their derivatives are the most potent inhibitors known of the NA-uptake process of central and peripheral NA-neurons. No other biochemical effect of these drugs which is remotely comparable in potency to this has been discovered. It is tempting to suppose, therefore, that the behavioural actions of these drugs are related to an inhibition of NA uptake. Such an inhibition would be expected to potentiate the actions of NA after its release at central noradrenergic synapses, and would imply that depression is associated in some way with a deficiency or hypoactivity of noradrenergic neurons. Unfortunately, however, this remains still an attractive hypothesis with little experimental support... 

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