Attention norepinephrine

The exact cause of attention-deficit hyperactivity disorder is unknown, but dysfunction in neurotransmitters norepinephrine and dopamine has been implicated as a key component. 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

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. 

SSRI = selective serotonin reuptake inhibitor SNRI = serotonin norepinephrine reuptake inhibitor ARB = angiotensin receptor blocker ACE = angiotensin converting enzyme COX-2 = cyclooxygenase 2 ADHD = attention deficit hyperactivity disorder. 

The most successful treatments for ADHD have been those that increase the activity of the neurotransmitters dopamine and norepinephrine. It has been known for some time that our brains nse these two substances to focns attention during response to challenging or stressfnl situations. The theory that medications that increase the activity of either dopamine and/or norepinephrine would be good treatments for ADHD has largely proved true, and we now have medications that can help children and adults with ADHD tremendously. 

Tricyclic Antidepressants (TCAs). The TCAs have been nsed to treat ADHD for 30 or more years. Most often used are imipramine (Tofranil) and desipramine (Norpramin), mainly becanse they are the TCAs that most specihcally increase norepinephrine activity. Remember, boosting norepinephrine activity in the brain shonld improve attention. Other TCAs, namely, amitriptyline (Elavil, Endep) and nortriptyline (Pamelor), have been used, though they also increase norepinephrine activity. TCAs do offer a modest benefit for both the inattention and the hyperactivity of ADHD. In addition, they are often effective at doses mnch lower than those required to treat depression. However, their effectiveness nsnally falls short of the stimulant medications. In addition, TCAs have considerable side effects including dry mouth, constipation, drowsiness, weight gain, and adverse cardiac effects. 

Despite these alternatives, there are a few patients who cannot tolerate stimulants or who may be susceptible to abusing them. In such cases, the alternatives are limited. The best treatments for poor attention (in lieu of the stimulants) are antidepressants that boost norepinephrine and/or dopamine activity in the brain. Currently, this includes the TCAs, MAOls, and possibly venlafaxine or duloxetine. 

There is no place anymore for the amphetamines in our therapeutic armamentarium. The only indications for the other stimulants, modaflnil and methylphenidate, are respectively narcolepsy and the attention deflcit disorders (ADHD) and hyperactivity syndromes in children. Their mechanisms of action include enhanced release of dopamine and norepinephrine, re-uptake inhibition of dopamine and norepinephrine and to some extend monoamine oxidase inhibition. 

Mechanism of Action A CNS stimulant that blocks the reuptake of norepinephrine and dopamine into presynaptic neurons, increasing the release of these neurotransmitters into the synaptic cleft. Therapeutic Effect Decreases motor restlessness and fatigue increases motor activity, mental alertness, and attention span elevates mood. 

Figure 2.1 Fear responses involve the activation of many brain areas. The hypothalamus controls physical changes in the body, such as increased blood pressure and dilated pupils. The central gray area causes freezing behavior, the reticular net triggers a reflex response, and norepinephrine increases attention.

There is a lot of evidence that the major neurotransmitter system affected by benzodiazepines is the one that controls the release of the neurotransmitter norepinephrine (also known as noradrenaline). Studies suggest that people with anxiety illnesses have increased release of norepinephrine and that this continued release causes a depletion of this neurotransmitter and a shutdown of the neurons that are releasing it. This is important because norepinephrine is involved in making an animal or person focused or attentive to what is going on in the environment. When this neurotransmitter is overreleased, it causes anxiety. When no more norepinephrine is available for release, it causes a feeling of exhaustion. 

Norepinephrine (also called noradrenaline)—Controls emotional arousal and increases attention. 

Bymaster FP, Katner JS, Nelson DL, et al Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat a potential mechanism for efficacy in attention-deficit/hyperactivity disorder. Neuropsychopharmacology 27 699-711, 2002... 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

Stimulants increase the overall activity of the nervous system by boosting the release of various neurotransmitters such as dopamine, norepinephrine, and glutamate. The result is increased alertness, attention, and energy. Unfortunately, prescription stimulants can be highly addictive and cause cardiovascular side effects (increased heart rate, blood pressure, and irregular heart rate) as well as respiratory side effects (dilated airways and increased breathing rate). Taking stimulants repeatedly and in excessive doses can... 

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