Norepinephrine metabolic effects

Mechanism of Action Although its exact mechanism of action is unknown, this non-barbiturate is thought to bind to serotonin and dopamine receptors in the CNS. The drug may also increase norepinephrine metabolism in the locus ceruleus. Therapeutic Effect Decreased anxiety... 

Adrenal medulla Epinephrine, Norepinephrine Vascular and metabolic effects that facilitate increased physical activity... 

Atomoxetine increases the brain concentrations of norepinephrine. Adverse effects (constipation, dry mouth, nausea, fatigue, decreased appetite, insomnia, chest pain, palpitations, anxiety, erectile dysfunction, mood swings, nervousness and urinary retention) are more common in poor metabolizers of CYP2D6, as atomoxetine is metabolized through the cytochrome CYP2D6 pathway. 

The metabolic effects of epinephrine are important during injury. Epinephrine can activate purine metabolism and may contribute to the increased excretion of nitrogen after injury (G9). Epinephrine and norepinephrine promote chemical thermogenesis after injury and thus will contribute to the increased metabolic expenditure of the injury period (S7). Epinephrine will also cause an acute lowering of the plasma albumin with a rise in the a-globulin fraction probably due to the effect on ACTH secretion. 

Norepinephrine Tyr Peripheral nerve endings adrenal medulla Yes Cardiovascular and metabolic effects (via a- and )3-adrenergic receptors). 

The actions of epinephrine and norepinephrine in the liver, the adipocyte, the skeletal muscle cell, and the a and 3 cells of the pancreas direcdy influence fuel metabolism (Fig. 43.6). These catecholamines are counterregulatory hormones that have metabolic effects directed toward mobilization of fuels from their storage sites for oxidation by cells to meet the increased energy requirements of acute and chronic stress. They simultaneously suppress insulin secretion, which ensures that fuel fluxes will continue in the direction of fuel utilization rather than storage as long as the stressful stimulus persists. 

In a third study the time course of the effects of intravenous and intracoronary injections of cysteinyl leukotrienes on metabolic parameters and systemic and coronary hemodynamics was examined in patients with normal coronary arteries [32]. LTD4 (3 nmol, injected into the left coronary artery) induced an early (20 s), transient fall in mean arterial pressure paralleled by rises in heart rate and plasma levels of epinephrine and norepinephrine, all of which had returned to baseline by 10 min. CVR rose at 10 and 15 min and myocardial oxygen extraction at 15 min. Thus, small doses of cysteinyl leukotrienes may induce both an early, transient fall in mean arterial pressure, with secondary sympathoadrenergic activation, and a later increase in small coronary arteriolar resistance. 

MAOI (Monoamine Oxidase Inhibitors) will intensify and prolong the effects of NN-DMT, however this is never recommended. Foolish combinations of MAOIs and other drugs can lead to serious health problems and even death. The tryptamines are normally metabolized by an MAO in the body. MAO metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this, MAOIs increase levels of those neurotransmitters. Tyramine will not be metabolized and will cause an increase in tyramine levels in blood. 

The profound effects of Li+ upon phosphoinositide metabolism and cell signaling have been the subject of several recent reviews [54,81,85,86]. These effects are dependent upon receptor stimulation of the phosphoinositide cycle by a range of stimuli, including norepinephrine, serotonin, and carbachol the basal turnover of this cycle is largely unaffected by Li+ [82,87,88]. 

The Rauwolfia alkaloid reserpine, due to its strong central component of activity, is excluded from this review, even though it has the peripheral effect of releasing norepinephrine from storage sites where it can be metabolized by monoamine oxidase. This results in neurotransmitter depletion and it appears that good blood pressure control would be achieved by a drug which has this peripheral mechanism but lacks the central component. The Mead-Johnson compound MJ-10459-2 (LXI) shows activity in... 

Costa LG, KaylorG, Murphy SD. 1986. Carbachol-and norepinephrine-stimulated phosphoinositide metabolism in rat brains Effect of chronic cholinesterase inhibition. J Pharmacol Exp Ther 239 32-37. 

The MAO enzymes, which come in two types known as MAO-A and MAO-B, perform a scavenger function by metabolizing and thereby eliminating certain molecules from nerve cells. This prevents the accumulation of toxic levels of these substances. In the brain, the MAO-A enzyme metabolizes a variety of substances including norepinephrine and serotonin, and the MAO-B enzyme metabolizes dopamine and several other substances. The effectiveness of MAOIs primarily comes from their ability to inhibit the MAO-A enzyme and thereby boost the availability of norepinephrine and serotonin. 

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stim-ulating effect in addition to its peripheral actions. The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with aU indirectly acting adrenomimetic amines,... 

C. Amphetamine is an indirectly acting adrenomimetic amine that depends on the release of norepinephrine from noradrenergic nerves for its action. Tlius, its effect depends on neuronal uptake (blocked by cocaine) to displace norepinephrine from the vesicles and the availability of norepinephrine (depleted by reserpine). The substitution on the a-carbon atom blocks oxidation by monoamine oxidase. With no substitution on its benzene ring, amphetamine resists metabolism by COMT. 

Corticosteroids also affect adrenomeduUary function by increasing epinephrine production the mechanism is exertion of a stimulatory action on two of the enzymes that regulate catecholamine synthesis, tyrosine hydroxylase, the rate-Umiting enzyme, and phenyl-ethanolamine Af-methyltransferase, which catalyzes the conversion of norepinephrine to epinephrine. Steroids also influence the metabolism of circulating catecholamines by inhibiting their uptake from the circulation by noimeuronal tissues (i.e., extraneuronal uptake see Chapter 9). This effect of corticoids may explain their permissive action in potentiating the hemodynamic effects of circulating catecholamines. 

The norepinephrine transporter (NET) and the vesicular monoamine transporter (VMAT) are presynaptic components of the sympathetic neurons. NET is a Na+ /Cl -dependent transport protein and responsible for the neurotransmitter uptake from the synaptic cleft into the cytoplasm of the neurons. This transport process, called uptake-1, reduces the amount and, thus, the effect of NE released into the synaptic cleft. NE is stored in the cytoplasm of the neurons in specialized vesicles by the H+-dependent transport protein VMAT. Two isoforms VMAT1 and VMAT2, are known. VMAT is localized in the vesicle membranes, and the vesicular storage protects NE from metabolism by monoamine oxidase (MAO), which is localized on the surface membrane of the mitochondria. Vice versa, nerve depolarisation causes NE release from the vesicles into the synaptic cleft by Ca+-mediated exocytose (Fig. 12) [79,132-136],... 

Mechanism of Action A sympathomimetic amine that stimulates the release of norepinephrine and dopamine. Therapeutic Effect Decreases appetite. Pharmacokinetics Rapidly absorbed from the gastrointestinal (GI) tract. Widely distributed. Metabolized in liverto active metabolite and undergoes extensive first-pass metabolism. Excreted in urine. Unknown if removed by hemodialysis. Half-life 4-6 hr. 

Mechanism of Action An antidepressant that appears to inhibit serotonin and norepinephrine reuptake at CNS neuronal presynaptic membranes is a less potent inhibitor of dopamine reuptake. Therapeutic Effect Relieves depression. Pharmacokinetics Well absorbed from the G1 tract. Protein binding greater than 90%. Extensively metabolized to active metabolites. Excreted primarily in urine and, to a lesser extent, in feces. Half-life 8-17 hr. 

Mechanism of Action Atricyclicantidepressant, antineuralgic, andantineuriticagent that blocks the reuptake of neurotransmitters, such as norepinephrine and serotonin, at presynaptic membranes, increasing their concentration at postsynaptic receptor sites. Therapeutic Effect Relieves depression and controls nocturnal enuresis. Pharmacokinetics Rapidly, well absorbed following PO administration. Protein binding more than 90%. Metabolized in liver, with first-pass effect. Excreted in urine as metabolites. Half-life 6-18 hr. 

Mecfianism of Action A phenylalkylamine sympathomimetic with activity similar to amphetamines that stimulates the central nervous system (CNS) and elevates blood pressure (BP) most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreases appetite. Pharmacokinetics The pharmacokinetics of phendimetrazine tartrate has not been well established. Metabolized to active metabolite, phendimetrazine. Excreted in urine. Half-life 2-4 hr. 

Mechanism of Action A sympathomimetic amine structurally similar to dextroamphetamine and is most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreased appetite. 

Mechanism of Action A central nervous system (CNS) stimulant that inhibits re-uptake of serotonin (enhancing satiety) and norepinephrine (raises metabolic rate) centrally. Therapeutic Effect Induces and maintains weight loss. 

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