Norepinephrine stability

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. 

There is evidence for the contribution of serotonin dysfunction to mania, and in the mechanism of action of mood stabilizers [19], however, specific data on the serotonergic system and mania are fewer and variable. Moreover, altered functioning of other neurotransmitters in mania such as norepinephrine, dopamine, acetylcholine, and GABA, and their interaction with serotonin, are also likely to be involved in the pathogenesis of mood disorders. Differences in these neurotransmitter systems possibly underlie differences in the pathogenesis of depressive and manic episodes. 

If we dehne a mood stabilizer as a medication that is both an effective anti-manic and antidepressant, then lithium arguably remains to this day the prototypical mood stabilizer. Lithium not only reduces the symptoms of acute BPAD, it also prevents the recurrence of additional mood episodes. Despite the fact that lithium has revolutionized the treatment of BPAD and remains nearly 50 years after its introduction as the single best treatment for many patients with BPAD, there is still no consensus as to how it works. Lithium exerts effects on several neurotransmitter systems (e.g., serotonin, dopamine, norepinephrine, acetylcholine), on second messenger systems inside the nerve cell, and on nerve cell gene expression. Yet, precisely how these varied effects produce lithium s therapeutic benefit remains unclear. 

It appears that SSRls and bnpropion are less likely than TCAs to indnce mania. Venlafaxine, perhaps becanse of its dnal effects on serotonin and norepinephrine like the TCAs, also appears to increase the likelihood of switching into mania. Rarely, if ever, shonld an antidepressant be nsed in bipolar patients withont concomitant treatment with a mood stabilizer. 

Nitrosonaphtholsulfonic adds, stability constants of metal Comdexes, 278 Nitrotoluene, 182,183 Nonane, 173 Nonanoic acid, 260 Nonionk sur ctants, 296 Noradrenaline, 231,264 Norephrine, 264 Norepinephrine, 284 Norcihistereone, 297 DL-Norleudne, resdution of, 262 Normetanephiine, 223, 231... 

Mechanism of Action A mood stabilizer that affects the storage, release, and reuptake of neurotransmitters. Antimanic effect may result from increased norepinephrine re-uptake and serotonin receptor sensitivity. Therapeutic Effect Produces antimanicand antidepressant effects. 

Swann AC Norepinephrine and (Na, K )-ATPase evidence for stabilization by lithium or imipramine. Neuropharmacology 27 261-267, 1988... 

Hydantoins Ethotoin (Peganone) Fosphenytoin (Cerebyx) Mephenytoin (Mesantoin) Phenytoin (Dilantin) Primary effect is to stabilize membrane by blocking sodium channels in repetitive-firing neurons higher concentrations may also influence concentrations of other neurotransmitters (GABA, norepinephrine, others)... 

Mechanism of Action. These drugs are believed to exert their primary antiepileptic effects in a manner similar to phenytoin—that is, they stabilize the neuronal membrane by slowing the recovery of sodium channels firing too rapidly. Carbamazepine may also inhibit the presynaptic uptake and release of norepinephrine, and this effect may contribute to its antiseizure activity. 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

At high concentrations, phenytoin also inhibits the release of serotonin and norepinephrine, promotes the uptake of dopamine, and inhibits monoamine oxidase activity. The drug interacts with membrane lipids this binding might promote the stabilization of the membrane. In addition, phenytoin paradoxically causes excitation in some cerebral neurons. A reduction of calcium permeability, with inhibition of calcium influx across the cell membrane, may explain the ability of phenytoin to inhibit a variety of calcium-induced secretory processes, including release of hormones and neurotransmitters. The significance of these biochemical actions and their relationship to phenytoin s clinical activity are unclear. 

Increased production of metabolites of phenylalanine that inhibit synthesis of a variety of substances required for normal brain growth Inhibition of TV-methyl-D-aspartate receptors, which are involved in memory and learning Competitive inhibition of transport of other amino acids required for protein synthesis Impaired polyribosome formation or stabilization Reduced synthesis/increased degradation of myelin Decreased formation of norepinephrine and serotonin Altered myelin structure and function... 

Li et al. [77] reported the electrocatalytic oxidation of norepinephrine at a GCE modified with SWCNTs. The electrode showed a very good reproducibility and stability. A linear relationship was obtained between the oxidation peak current and norepinephrine concentration between 1.0 x 10 and 1.1 x 10" M and the detection limit was 6.0 x 10 M. The electrocatalytic activity of the SWCNTs-modified-GCE was also demonstrated with dopamine, epinephrine and ascorbic acid. 

In intensive care settings, sympathomimetic catecholamines [e.g., dobutamine, dopamine, epinephrine (adrenaline), isoprenaline (isoproterenol), norepinephrine (noradrenaline, and levarterenol] are often administered via continuous infusion. In clinical practice, reservoirs and administration sets of these drugs are routinely changed every 12 or 24 hours. As the pharmacological efficacy of catecholamines is directly related to their intact phenolic groups, their stability over these dosing periods is questionable. 

Adrenaline acid tartrate (0.4mg/L in normal saline and packaged in polypropylene syringes) exposed for 24 hours to ambient illuminating conditions also showed no loss of potency (78). However, various epinephrine preparations may vary in their stability, depending on the form of epinephrine as well as the preservatives and packaging used. Hoechst (today, Sanofi-Aventis) claims that, according to their experimental studies, diluted solutions (0.2,1,2mg/L) of Arterenol (norepinephrine HCL) and Suprarenin (epinephrine HCL) are stable for up to 24 hours in polypropylene syringes, if stored without photoprotection. 

Phenytoin is a hydantoin derivative like dantrolene and the oldest non-sedative anticonvulsant drug known. It alters sodium, potassium and calcium conductance across cell membranes thereby altering membrane potentials and amino acid and neurotransmitter concentrations (i.e. norepinephrine (noradrenaline), acetylcholine and GABA). Its major mode of action appears to be the blockade of sodium channels and e inhibition of the generation of repetitive action potentials (membrane stabilization) (see Chs 9 and 12). 

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