Norepinephrine drugs affecting

One can simply classify a drug as noradrenergic on the basis of interaction with the transporter or specific receptor subtypes. But this does not really address the functional consequences, such as the extent to which, for instance, a drug affects the intrasynaptic concentration of norepinephrine. The latter requires some knowledge of the pathway followed by norepinephrine from synthesis, storage, release, and clearance. This pathway is depicted in Figure 15-1. 

Norepinephrine is used pharmacologically for its ability to cause peripheral vasoconstriction and increase blood pressure, which is useful to stem the effects of large drops in blood pressure as can occur in trauma or shock. Drugs affecting norepinephrine release and/or reuptake also have significant CNS utility, including the treatment of depression and attention deficit disorder. 

Table 1 Drugs affecting the storage, release, reuptake, autoregulation and metabolism of norepinephrine, (j), inhibitory effect ( ), excitatory effect.

Early formulations of the monoamine theory of depression cited two strands of evidence. One was the effects of antidepressant drugs and the other was the effects of reserpine. Skildkraut believed that studies have shown a fairly consistent relationship between drug effects on catechloamines, especially norepinephrine, and affective or behavioural states (Schildkraut 1965, p. 509). He went on to describe how drugs that cause depletion and inactivation of norepinephrine centrally produce sedation or depression, while drugs which increase or potentiate brain norepinephrine are associated with behavioural stimulation or excitement and generally exert an antidepressant effect in man (p. 509). 

The type of response normally elicited by glutamate, GABA, ACh, dopamine, norepinephrine, serotonin (5HT), and the opioid peptides and the modulations induced by drugs affecting the receptors relevant to each of these transmitters is succinctly presented. 

Methylphenidate is similar to amphetamine and, like amphetamine, stimulates the central nervous system (CNS), which consists of the brain and spinal cord. Stimulant drugs affect mood and alertness, and depress food appetite by increasing levels of several neurotransmitters in the brain. Although the exact therapeutic mode of action of methylphenidate is not known, the drug has been shown to elevate levels of some of these neurotransmitters, primarily dopamine and norepinephrine (noradrenaline). 

Drugs Affecting Norepinephrine Reiease, Reuptake, and Metaboiism... 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Dopamine, norepinephrine, and serotonin have other responsibilities in the body besides dictating hunger. For example, norepinephrine also helps control blood pressure. Drugs that affect the level of these neurotransmitters interfere with other body processes and produce negative side effects. A drug that increases norepinephrine will decrease appetite, but... 

The metabolism of norepinephrine is reported to be altered by other drugs used in the treatment of the affective disorders and a number of studies have shown a change in the metabolism of norepinephrine as a result of Li+ treatment. In rat brain, acute Li+ treatment enhances the uptake of norepinephrine in synaptosomes [151] and the enhanced turnover of this neurotransmitter may be due to an increase in its deamination in the brain, although Li+ also causes a slight increase in the levels of the amino acid precursor, tyrosine, in the brain and plasma of rats [152]. Also, acute Li+ treatment induces a decrease in the release of norepinephrine after electrical stimulation of rat brain [153]. Interest-... 

Traditionally, most affective disorders have been treated with compounds that resemble the neurotransmitters that are deficient or in excess in specific brain regions. The aberrant levels of neurotransmitters (or their receptors), such as norepinephrine, dopamine, acetylcholine, and serotonin, have correlated with behavioral symptoms of schizophrenia, depression, anxiety, sleep disorders, motor dysfunctions, attention difficulties, and cognitive disorders. Most drugs discovered for these disorders resulted from screening compounds directly in rodent behavioral models that mimic the behavior of the disease. In these cases, the molecular target" or mechanism of action was assumed to be the deficiency or excess of a neurotransmitter. 

Despite the fact that the initial biochemical abnormalities responsible for depression and manic-depressive conditions have not been completely discovered, some facts suggest that depressive conditions may be caused by a lack of norepinephrine (noradrenaline) and serotonin. The majority of drugs used in treatment of such illnesses act by affecting the system of biogenic amines of the brain, thus leading to action of a mechanism that is capable of increasing their contents in respective parts of the brain. 

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