Norepinephrine dopamine and

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Povlock, SL and Amara, SG (1997) The structure and function of norepinephrine, dopamine and serotonin transporters. In Neurotransmitter Transporters Structure, Function, and Regulation (Ed. Reith, MEA), Humana Press, Totowa, NJ, pp. 1-28. 

Weiss, JM, Goodman, PA, Lostito, BG, Corrigan, S, Charry, JM and Bailey, WH (1981) Behavioral depression produced by an uncontrollable stressor relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res. Rev. 3 167-205. 

Sixteen years later, when the first edition of Basic Neurochemistry appeared, Sol Snyder s chapter could classify norepinephrine, dopamine and serotonin as... 

Lakshmana MK, Trichur TR. 1997. An isocratic assay for norepinephrine, dopamine and 5-hydroxytryptamine using their native fluorescence by high-performance liquid chromatography with fluorescence detection in discrete brain areas of rat. Anal Biochem 246 166-170. 

Stolerman IP, Chamberlain S, Bizarro L, Fernandes C, Schalkwyk L (2004) The role of nicotinic receptor alpha7 subunits in nicotine discrimination. Neuropharmacology 46 363-371 Summers KL, Giacobini E (1995) Effects of local and repeated systemic administration of (—) nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex. Neurochem Res 20 753-759... 

The two pioneer drugs for schizophrenia are chlorpromazine and reserpine. Reserpine is known to reduce the brain levels of norepinephrine, dopamine, and serotonin. Since reserpine is also effective in coping with some of the symptoms of schizophrenia, perhaps an abnormally high concentration of one or more of these monoamines is a contributing factor to this disorder. 

Monoamine Oxidase Inhibitors (MAOIs). The MAOls work in a unique fashion by blocking the activity of an enzyme that degrades each of three key brain transmitters norepinephrine, dopamine, and serotonin. These widespread effects on several brain transmitter systems make the MAOls a potentially very effective class of medications for a variety of disorders. A few small studies have evaluated the usefulness of the MAOls in the treatment of BPD and found them moderately helpful for the impulsivity associated with this illness. Unfortunately, the requirements for strict dietary restrictions due to a risk of hypertensive crisis severely limit the usefulness of MAOls in the treatment of BPD. These restrictions are a particular concern when treating patients who have problems with impulsivity and are therefore likely to have difficulty maintaining the dietary regimen. For this reason, although they may theoretically be helpful, MAOls should only be used to treat BPD after other more easily tolerated medications have been tried and have failed. In the near future, so-called reversible MAOls that appear to avoid the need for diet restrictions may become available. If so, this will allow us to reconsider their use in the treatment of BPD. For more information regarding the use of MAOls, please refer to Chapter 3. 

Adrenergic neuron blockers cause degradation of biogenic amines in neuron endings. These drugs can interfere with the synthesis, storage and release of norepinephrine, dopamine, and serotonin. 

Reserpine causes a breakdown of norepinephrine, dopamine, and serotonin in neuron endings. It weakens intracellular uptake of biogenic amines and reduces the ability if storing them in vesicles. It is possible that reserpine acts on membrane vesicles, irreversibly inhibiting ATP-Mg (adenosinetriphosphate) requiring process that is responsible for the uptake of biogenic amines in intemeuronal vesicles. Breakdown of catecholamines is expressed by a decreased number of intraneuronal serotonin and dopamine. 

Reserpine canses release of norepinephrine, dopamine, and serotonin at nenronal termini. It weakens the intracellnlar uptake of biogenic amines and decreases the ability to store them in vesicles. 

Admixture incompatibilities - Avoid adding sodium bicarbonate to parenteral solutions containing calcium, except where compatibility is established precipitation or haze may result. Norepinephrine, dopamine, and dobutamine are incompatible. 

Isogawa K, Akiyoshi J, Hikichi T, Yamamoto Y, Tsutsumi T, Nagayama H (2000) Effect of corticotropin releasing factor receptor 1 antagonist on extracellular norepinephrine, dopamine and serotonin in hippocampus and prefrontal cortex of rats in vivo. Neuropeptides 34 234-239... 

Reserpine also interferes with the neuronal storage of a variety of central transmitter amines such that significant depletion of norepinephrine, dopamine, and 5-hydroxytryptamine (serotonin) occurs. This central transmitter depletion is responsible for the sedation and other CNS side effects associated with reserpine therapy. The depletion of brain amines also may contribute to the antihypertensive effects of reserpine. 

The enzyme MAO metabolizes some of the neurotransmitters affected by some drugs of abuse, namely epinephrine, norepinephrine, dopamine, and serotonin. Dangerously high levels can result if an inhibitor of this enzyme, or monoamine oxidase inhibitor (MAOI), is used along with the drug of abuse. 

Pharmacologic targeting of monoamine transporters. Commonly used drugs such as antidepressants, amphetamines, and cocaine target monoamine (norepinephrine, dopamine and serotonin) transporters with different potencies. A shows the mechanism of reuptake of norepinephrine (NE) back into the noradrenergic neuron via the norepinephrine transporter (NET), where a proportion is sequestered in presynaptic vesicles through the vesicular monoamine transporter (VMAT). and C show the effects of amphetamine and cocaine on these pathways. See text for details. 

Many inhibitors of the amine transporters for norepinephrine, dopamine, and serotonin are used clinically. Although specificity is not absolute, some are highly selective for one of the transporters. Many antidepressants, particularly the older tricyclic antidepressants can inhibit norepinephrine and serotonin reuptake to different degrees. This may lead to orthostatic tachycardia as a side effect. Some antidepressants of this class, particularly imipramine, can induce orthostatic hypotension presumably by their clonidine-like effect or by blocking 04 receptors, but the mechanism remains unclear. 

The first generation of antidepressants, MAO (monoamine oxidase) inhibitors, inhibited neurotransmitter degradation by inhibiting monoamine deoxidase, a flavin containing enzyme, found in the mitochondria of neurons and other cell types, that oxidatively deaminates naturally occurring sympathomimetic monoamines, such as norepinephrine, dopamine, and serotonin within the presynapse. In 1952, isoniazid and its isopropyl derivative, iproniazid (1), were developed for the treatment of tuberculosis, where it was subsequently found that these agents had a mood enhancing effect on... 

Acetylcholine is destroyed too quickly and completely by AChE to be available for transport back into the presynaptic neuron, but the choline that is formed by its breakdown can be transported back into the presynaptic cholinergic nerve terminal by a transporter similar to the transporters for other neurotransmitters discussed earlier in relation to norepinephrine, dopamine, and serotonin neurons. Once back in the presynaptic nerve terminal, this choline can be recycled into acetylcholine synthesis (Fig. 12—8). 

Ginseng inhibits the uptake of GABA, glutamate, norepinephrine, dopamine, and serotonin. 

Sibutramine (Meridia) is introduced as a weight-loss drug. Sibutramine inhibits the reuptake of the brain chemicals norepinephrine, dopamine, and serotonin, but does not promote monoamine release like the amphetamines. 

Sibutramine (Meridia), a weight-loss drug introduced in 1998, inhibits the reuptake of the brain chemicals norepinephrine, dopamine, and serotonin, but does not promote monoamine release like the amphetamines. Yet the drug has been linked to serious side effects, including rapid heart rate, increased blood pressure, heart disease, stroke, seizure, and mental impairments. In March 2002, Italy s Health Ministry announced that it was immediately withdrawing all sibutramine products from the market due to health-related problems. Also, Meridia was the subject of a class action lawsuit filed in the United States. 

Reserpine blocks the ability of aminergic transmitter vesicles to take up and store biogenic amines, probably by interfering with an uptake mechanism that depends on Mg2+ and ATP (Figure 6-4, carrier E). This effect occurs throughout the body, resulting in depletion of norepinephrine, dopamine, and serotonin in both central and peripheral neurons. Chromaffin granules of the adrenal... 

Based on the findings that 2,3,7,8-TCDD administered into the lateral cerebral ventricles does not cause death or decreased feed intake in rats (Stahl and Rozman 1990), Rozman et al. (1991) examined the possibility that 2,3,7,8-TCDD suppresses appetite via peripheral mechanisms acting on the central nervous system. The results of experiments of transfusion of blood from rats with 2,3,7,8-TCDD-induced appetite suppression and normal satiated rats suggested that 2,3,7,8-TCDD-treated rats are not satiated, rather than that they are not hungry. In a second experimental series, the possible role of norepinephrine, dopamine, and serotonin as central mediators of appetite suppression induced by... 

The principal groups of antidepressants available today are all presumed to exert their action via alteration of brain monoamine metabolism. These amines include norepinephrine, dopamine, and serotonin. The involvement of catecholamines in the pathogenesis of depression was invoked as early as 1965. A deficiency in brain serotonin was theorized in 1967, while a role for dopamine in depression was formally proposed in 1975. The drugs that are used to treat depression basically act to increase neurotransmitter concentration in the synaptic cleft either by (1) decreasing neurotransmitter degradation or (2) inhibiting neurotransmitter reuptake. 

Monoamine oxidase (MAO) is a mitochondrial enzyme found in neural and other tissues, such as the gut and liver. In the neuron, MAO functions as a safety valve to oxidatively deaminate and inactivate any excess neurotransmitter molecules (norepinephrine, dopamine, and serotonin) that may leak out of synaptic vesicles when the neuron is at rest. The MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and therefore to both accumulate within the presynaptic neuron and to leak into the synaptic space. This causes activation of norepinephrine and serotonin receptors, and may be responsible for the antidepressant action of these drugs. Three MAO inhibitors are currently available for treatment of depression phenelzine [FEN el zeen], isocarboxazid [eye soe kar BOX a zid], and tranylcypromine [tran ill SIP roe meen] no one drug is a prototype. Use of MAO inhibitors is now limited because of the complicated dietary restrictions required of patients taking MAO inhibitors. 

In an attempt to shed light on the mechanism by which neuroleptics induce extrapyramidal reactions, Bishnoi et al. (2007) chronically administered haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) to rats, resulting in a time-dependent increase in orofacial hyperkinetic movements. They found a corresponding time-dependent decrease in extracellular levels of norepinephrine, dopamine, and serotonin in various cortical and subcortical regions of the brain. 

Metabolism. Histamine-storing cells form histamine by decarboxylation of the amino acid histidine. Released histamine is degraded no reuptake system exists as for norepinephrine, dopamine, and serotonin. 

Inhibitors of monoamine oxidase A (thy-meretics). Moclobemide is the only representative of this group. It produces a reversible inhibition of MAOa, which is responsible for inactivation of the amines norepinephrine, dopamine, and serotonin (A). Enzyme inhibition results in an increased concentration of these neurotransmitters in the synaptic cleft. Moclobemide is less effective as an antidepressant than as a psychomotor stimulant. It is indicated only in depressions with extreme psychomotor slowing and is contraindicated in patients at risk of suicide. 

Again, there are various dmgs with different ranges and specificities. Cocaine has a particularly broad spectrum, affecting the reuptake of norepinephrine, dopamine, and serotonin alike. The effect of cocaine can be quantitatively studied in mice by observing their excitement in response to being placed into a new environment, which is measured simply as the distance travelled within their new home over time. In experiments with transgenic mice, the reuptake transporters for both dopamine and serotonin had to be deleted in order to abolish the increase in excitement induced by cocaine. 

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