Monoamine oxidase with dopamine

The COMT inhibitors should not be administered with the monoamine oxidase (MAO) inhibitors (see Chap. 31) because there is an increased risk of toxicity. If the COMT inhibitors are administered with norepinephrine, dopamine, dobutamine, methyldopa, or epinephrine, there is a risk of increased heart rate, arrhythmias, and excessive blood pressure changes. 

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. 

Monotherapy usually begins with a monoamine oxidase-B (MAO-B) inhibitor, or if the patient is physiologically young, a dopamine agonist. 

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. 

A third way of promoting norepinephrine activity is to interfere with the enzyme that inactivates norepinephrine, monoamine oxidase (MAO). The monoamine oxidase inhibitors (MAOIs) work in this way. Incidentally, inhibiting monoamine oxidase also increases serotonin and dopamine activity. 

The major routes for the synthesis and metabolism of noradrenaline in adrenergic nerves [375], together with the names of the enzymes concerned, are shown in Figure 3.1. Under normal conditions the rate controlling step in noradrenaline synthesis is the first, and the tissue noradrenaline content can be markedly lowered by inhibition of tyrosine hydroxylase [376]. Tissue noradrenaline levels can also be lowered, but to a lesser extent, by inhibition of dopamine-(3-oxidase [377, 378]. However, the noradrenaline depletion produced by guanethidine is unlikely to result from inhibition of synthesis, since intra-cisternal injection of guanethidine does not prevent the accumulation of noradrenaline which follows brain monoamine oxidase inhibition, even though it does cause depletion of brain noradrenaline [323]. 

Drugs that may interact with linezolid include monoamine oxidase inhibitors, SSRIs, and adrenergic agents (eg, dopamine, epinephrine). 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

Dopamine metabolism inhibitors interfere with monoamine oxidase and catecholamine-0-methyltransferase. Monoamine oxidase will be discussed separately in chapter 8. 

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. 

The effect of dopamine is prolonged and intensified by monoamine oxidase inhibitors (MAOIs). If dopamine must be administered to a patient on these drugs, the dose should be reduced to one-tenth or less of that normally used. Concomitant medication with tricyclic... 

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