Neurotransmitter dopamine

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

The immediate metabolic precursor to dopamine, l-DOPA (L-dihydroxphenylalanine) is converted to the active neurotransmitter dopamine by the action of the enzyme aromatic amine acid decarboxylase (AADC). l-DOPA (INN name Levodopa) is the main diug used to treat Parkinson s disease. 

Acute treatment with nonselective MAO inhibitors (iproniazid, tranylcypromine, phenelzine), as a consequence of inhibiting both forms of the enzyme, increase, brain levels of all monoamines (phenylethylamine, tryptamine, methylhistamine aminergic neurotransmitters (dopamine, noradr enaline, adrenaline and serotonin). By contrast MAO-A inhibitors (clorgyline) increase serotonin and noradrenaline, while MAO-B inhibitors (selegiline, rasagiline) increase brain levels... 

Describe the rationale of using electrodes coated with Nation films for selective detection of the cationic neurotransmitter dopamine in the presence of the common interference from anionic ascorbic acid. 

Figure 13.7 Synthesis and structure of the trace amines phenylethylamine, /)-tyramine and tryptamine. These are all formed by decarboxylation rather than hydroxylation of the precursors of the established monoamine neurotransmitters, dopamine and 5-HT. (1) Decarboxylation by aromatic L-amino acid decarboxylase (2) phenylaline hydroxylase (3) tyrosine hydroxylase (4) tryptophan hydroxylase...

The neurotransmitters dopamine and serotonin are the likely mediators of this effect. 

In the brain, methamphetamine causes massive amounts of the neurotransmitters dopamine, norepinephrine, and serotonin to be released from neurons in the brain, particularly in the limbic system and frontal cortex. Scientists believe the increased dopamine release in these brain regions is responsible for methamphetamine s ability to keep people awake, alert, energetic, active, and possibly addicted. Methamphetamine acts on a variety of brain regions to produce a number of different effects (Table 2.1). 

Monoamine The primary psychoactive mechanism of cocaine is blocking reuptake of the monoamine neurotransmitters dopamine, norepinephrine, and serotonin, leading to increased available synaptic transmitters (O Brien 1996). Chronic use is associated with changes in... 

Human HRS encoded by a gene, which consists of four exons on chromosome 20, was demonstrated in 1987 and cloned recently [17]. HRS has initially been identified in the central and peripheral nervous system as presynaptic receptors controlling the release of histamine and other neurotransmitters (dopamine, serotonin. 

Hao C, March RE, Croley TR, Chen S, Legault MG, et al. 2002. Study of the neurotransmitter dopamine and the neurotoxin 6-hydroxydopamine by electrospray ionization coupled with tandem mass spectrometry. Rapid Commun Mass Spectrom 16 591. 

Tyrosine is also the metabolic precursor to the neurotransmitter dopamine and the catecholamine hormones norepinephrine (noradrenaline) and epinephrine (adrenaline), as well as to the alkaloids in opium, including morphine. 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

In the human CNS, glutamate is the most important excitatory neurotransmitter. Glycine is a major inhibitory neurotransmitter in the human CNS. Thus, these two amino acids, basic constituents of proteins, also function in other very important ways in behavior, emotion, learning, memory, and sensory perception. Nature uses its molecular constructs for more than one purpose. Among other neurotransmitters, dopamine, epinephrine, norepinephrine, and serotonin are derivatives of protein amino acids and are synthesized from them. 

Too Much Neurotransmission. Other mental illnesses result from too much neurotransmission (i.e., overactivity) of certain brain circuits. One example may be psychosis, for example, hallucinations and delusions that have been hypothesized to result from excessive transmission of the neurotransmitter dopamine in certain pathways. In some cases, the transmission becomes so excessive that it kills the nerve cell, a phenomenon called excitotoxicity. This process is believed to occur in some patients with epilepsy and in those with Huntington s disease. 

Neurotransmitter Precursors. Most neurotransmitters are manufactured by the neurons themselves from a variety of simple building block substances that are commonly obtained from the diet. Another way to promote neurotransmission is to increase the available pool of neurotransmitter by supplementing the supply of a precursor substance. In most instances, this is a very inefficient and largely ineffective approach to treatment. However, L-DOPA, the immediate precursor to the neurotransmitter dopamine, remains an effective treatment for Parkinson s disease. 

The nigrostriatal pathway participates in the production of smooth physical motion. It is not the brain area that works to initiate movement, which is in the cerebral cortex (pyramidal tract) it is the region that helps one to have fluid motion (extrapyramidal tract). Although many neurotransmitters are found in this latter system, two neurotransmitters—dopamine and acetylcholine—are predominantly involved in this pathway. The brain normally maintains a relatively stable ratio of dopamine and acetylcholine in the pathway. However, when something happens to upset this ratio, problems arise. 

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. 

This procedure has some similarity to that used to overcome a deficiency of the enzyme that synthesise the neurotransmitter dopamine in the brain. The deficiency gives rise to Parkinsons disease (Chapter 14). (Figure... 

An alternative delivery strategy for small molecules is based on the presence of the nutrient transporters. Drugs that are structurally similar to substrates of a carrier system can undergo facilitated brain uptake as pseudoneutrients. The best example of this is the therapeutic use of L-DOPA in Parkinson s disease. Unlike the neurotransmitter dopamine itself, which cannot cross the BBB in significant amounts, its precursor L-DOPA is a substrate for LAT, the transporter of large neutral amino acids [56]. Its uptake by the brain is saturable, and subject to competition by the other substrates of the carrier present in plasma. 

Some mental disorders also appear to result from disruption of the natural flow of neurotransmitters between neurons. For example, scientists now believe that the disorder known as Parkinson s disease may result from a deficiency of the neurotransmitter dopamine. Parkinson s disease is characterized by muscular rigidity, tremor while the person is at rest, difficulty in initiating movement (a condition known as hradykinesia), slowness of voluntary movement, difficulty with balance, and difficulty with walking. When the neuronal cells that produce dopamine begin to deteriorate, they release less of the neurotransmitter the normal flow of dopamine between cells is reduced and disruptions of normal nerve patterns develop, as evidenced by the symptoms described. 

Fluorinated dihydroxyphenylalanine p F]DOPA is a precursor for the neurotransmitter dopamine and is commonly used in the imaging of Parkinson s disease. In oncological imaging [ F]DOPA has been assessed for imaging of brain tumors, advanced neuroendocrine tumors and medullary thyroid cancer [215],... 

Atypical antidepressants such as Wellbutrin simultaneously target the neurotransmitters dopamine and norepinephrine. 

About the same time as the reserpine finding, physicians noticed that some of the drugs used to treat other diseases appeared to have a beneficial side effect—raising the patient s mood. Upon further testing, a chemically modified version of one of these drugs effectively reduced the symptoms of depressed patients. This drug, iproniazid, inhibits MAO, the enzyme that destroys the monoamine neurotransmitters— dopamine, norepinephrine, and serotonin. As a result, more of these... 

Another prevalent mental disorder, schizophrenia, has also had its share of various hypotheses and medications. Some of the most interesting research avenues involve the neurotransmitter dopamine. 

This approach is also applied successfully in Parkinson s disease. Drugs such as entacapone inhibit the activity of the enzyme catechol-omethyltransferase (COMT), which is involved in degradation of the neurotransmitter dopamine, and thus increase and prolong the availability of dopamine in the synaptic cleft. Inhibition of COMT and substitution of L-Dopa are often combined in the therapy of Parkinson patients. 

Carbon nanotube modified electrodes The electrochemical detection of the neurotransmitter dopamine is complicated by the high concentration of biologically coexisting ascorbic acid, which has an oxidation potential lying very close to dopamine s at solid... 

There has also been a report of activation of the estrogen receptor mediated by the neurotransmitter dopamine (Power et al., 1991). This mechanism of activation is independent of that by the hormone. 

Hydroquinones. - 3,4-Dihydroxyphenylacetic acid, a metabolite of the neurotransmitter dopamine, has been shown to undergo oxidation by "NO to a semiquinone, which was observed by EPR upon spin stabilisation with Mg2+ ions.119 Formation of the radical may be a crucial event in the development of Parkinson s disease (section 18.3). 4-Hydroxyestradiol, which has been implicated in breast cancer, is oxidised to a semiquinone by HRP. Mutagenicity is believed to result from addition of the quinone metabolite to DNA.120... 

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