Dopamine central nervous system

Central Nervous System. Dopamine monooxygenase (DMO) is an enzyme that requires copper, as a cofactor and uses ascorbate as an electron donor. This enzyme catalyzes the conversion of dopamine to norepinephrine, the important neurotransmitter. There are soluble and membrane-bound forms of the enzyme, the latter being found in the chromaffin granules of the adrenal cortex. Monoamine oxidase, one of the numerous amine oxidases, is a copper-containing enzyme that catalyzes the degradation of serotonin in the brain and is also involved in the metabolism of the catecholamines. 

Methyldopa, through its metaboHte, CX-methyInorepinephrine formed in the brain, acts on the postsynaptic tt2-adrenoceptor in the central nervous system. It reduces the adrenergic outflow to the cardiovascular system, thereby decreasing arterial blood pressure. If the conversion of methyldopa to CX-methyl norepinephrine in the brain is prevented by a dopamine -hydroxylase inhibitor capable of penetrating into the brain, it loses its antihypertensive effects. 

Show two methods for the synthesis of dopamine, a neurotransmitter involved in regulation of the central nervous system. Use any alkyl halide needed. 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

There is also evidence for ATP as a cotransmitter with y-aminobutyric acid or with glutamate, serotonin, NA or dopamine in nerves in the central nervous system. 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

As the rate-limiting enzyme, tyrosine hydroxylase is regulated in a variety of ways. The most important mechanism involves feedback inhibition by the catecholamines, which compete with the enzyme for the pteridine cofactor. Catecholamines cannot cross the blood-brain barrier hence, in the brain they must be synthesized locally. In certain central nervous system diseases (eg, Parkinson s disease), there is a local deficiency of dopamine synthesis. L-Dopa, the precursor of dopamine, readily crosses the blood-brain barrier and so is an important agent in the treatment of Parkinson s disease. 

Dopamine (5-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu " reduction back... 

The dramatic heightening of aggressive behavior in morphine-withdrawn animals may be due to dopamine receptor upregulation (Gianutsos et al. 1975 Lai et al. 1975). Morphine and methadone inhibit dopamine receptors in the central nervous system (CNS) suggesting possible disuse... 

Benkirane, S. Arbilla, S. and hanger, S.Z. A functional response to D1 dopamine receptor stimulation in the central nervous system Inhibition of the release of [ H]-serotonin from the rat substantia nigra. Naunyn-Schmiedebergs Arch Pharmacol 335 502-507, 1987. 

Ach, acetylcholine CNS, central nervous system CD, carbidopa COMT, catechol-O-methyltransferase D1, a class of dopamine receptors which includes D, and D5 subtypes D2, a class of dopamine receptors which includes D2, D3, and D4 subtypes DA, dopamine LD, levodopa MAO, monoamine oxidase MD, maintenance dose NMDA, N-methyl-D-aspartate. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

Phentermine decreases food intake, and hence weight, by increasing norepinephrine and dopamine release in the central nervous system. This drug is indicated for short-term use—no more than a few weeks—in addition to lifestyle modifications in obese patients with a BMI of 30 kg/m2 or greater or a BMI of 27 kg/m2" or greater in the presence of other risk factors.38... 

Synergy of unwanted pharmacological effect ginseng and its products will inhibit the central nervous system (CNS) when they are applied with luminal, chloral hydrate, or ephedrine, which can increase the release of dopamine, noradrenaline, and serotonin in the CNS thus inducing a hypertensive crisis if monoamine oxidase inhibitors (MAOIs) are given simultaneously. 

Rothman, R.B., Baumann, M.H., Dersch, C.M. et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 39 32, 2001. 

L-dopa is effective in the treatment of Parkinson s disease, a disorder characterised by low levels of dopamine, since L-dopa is metabolised into dopamine. However, this biosynthesis normally occurs in both the peripheral nervous system (PNS) and the central nervous system CNS. The related drug carbidopa inhibits aromatic L-amino acid decarboxylase only in the periphery, since it does not cross the blood-brain barrier. So, when carbidopa is given with L-dopa, it reduces the biosynthesis of L-dopa to dopamine in the periphery and, thus, increases the bioavailability of L-dopa for the dopaminergic neurons in the brain. Hence, carbidopa increases the clinical efficacy of L-dopa for Parkinsonian patients. 

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