Noradrenergic nerve ending

Dextroamphetamine is a powerful stimulant of the nervous system that manifests its effects by releasing dopamine and norepinephrine from presynaptic nerve endings, thus stimulating central dopaminergic and noradrenergic receptors. In certain doses it strengthens the excitatory process in the CNS, reduces fatigue, elevates mood and the capacity to work, reduces the need for sleep, and decreases appetite. 

Pharmacology Tetracyclics enhance central noradrenergic and serotonergic activity. They do not inhibit monoamine oxidase. Although maprotiline and mirtazapine are in the same chemical class, they each affect different neurotransmitters and thus have different side effect profiles. Maprotiline primarily acts by blocking reuptake of norepinephrine at nerve endings. 

Norepinephrine is widely distributed throughout brain in a nonuniform pattern, discrete from that of other amine systems such as dopamine and serotonin, although overlapping in several areas. The majority of noradrenergic axons and nerve endings found in the brain originate from the locus co-eruleus, a small, well-delineated cluster of cell bodies located in the pontine brain stem, just below the floor of the fourth ventricle. Given the wide distribution of norepinephrine in the brain [widely documented in the psychiatric literature), remarkably few neurons, estimated as 12,000 neurons on each... 

Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6-4. Presynaptic regulation by a variety of endogenous chemicals probably occurs in all nerve fibers. 

Clonidine, methyldopa Activate K-2 adrenoceptors Reduce central sympathetic outflow reduce norepinephrine release from noradrenergic nerve endings Hypertension clonidine also used in withdrawal from abused drugs Oral t clonidine also patch Toxicity sedation t methyldopa hemolytic anemia... 

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. 

Hydi oxydopaniine a neurohansmitter analogue that depletes noradrenergic stores in nerve endings and reduces dopamine levels in brain. Its mechanism of action is linked to cytolytic free-radical production. 

Reuptake inhibitor An indirectly acting drug that increases the activity of transmitters in the synapse by inhibiting their reuptake into the presynaptic nerve ending. May act selectively on noradrenergic, serotonergic, or both types of nerve endings... 

Alonso, M. J Arribas. S., Marin. J.. Balfagon, G., and Salaices, M. (1991), Presynapiie M2-muscarinic receptors on noradrenergic nerve endings and endothelium-derived M3 receptors in cat cerebral aneries. Brain Res. 567,76-82. 

Receptor interactions clonidine interacts at the G protein-coupled alpha receptors with a greater affinity for the alpha-2 receptors. The activation of the alpha-2 receptors results in decreased cAMP, K efflux as well as Ca entry into the nerve terminals. Activation of receptors in the sympathetic nerve endings and in the noradrenergic neurons in the CNS inhibits release of norepinephrine and may release acetylcholine. The locus coeruleus is an important modulator of alertness and may be the major site for the hypnotic effects of clonidine. Additionally, the G protein pathway has a similar transduction pathway to the opioids, explaining some of the cross-tolerance and synergy between the two classes of drugs. 

---