Highly neurotransmitter oxidation

The mechanism of antidepressive action of this series of drugs is likely associated with their inhibition of the oxidizing deamination process of the neurotransmitters norepinephrine, epinephrine, dopamine, and serotonin, which participate in the transmission of nerve excitement in the CNS. A major drawback of these drugs is the high toxicity associated with their inhibition of not only MAO, but also a number of other nonspecific enzymes. 

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... 

During clinical studies of iproniazid (201) in the treatment of tuberculosis it was found to have a mood-elevating effect. It was later found to be an inhibitor of monoamine oxidase (MAO), the enzyme which oxidatively deaminates such neurotransmitters as noradrenaline and serotonin, and it was tried in the treatment of depression in 1957. Other MAO inhibitors were introduced later, most of them being hydrazine derivatives. Heterocyclic examples include isocarboxazid (202) and nialamide (203). They are toxic and cause dangerous hypertensive crises if food with a high tyramine content is eaten, and on this account their use is limited. 

A quantitatively important pathway of cysteine catabolism in animals is oxidation to cysteine sulfinate (Fig. 24-25, reaction z),450 a two-step hydroxyl-ation requiring 02, NADPH or NADH, and Fe2+. Cysteine sulfinic acid can be further oxidized to cyste-ic acid (cysteine sulfonate),454 which can be decarbox-ylated to taurine. The latter is a component of bile salts (Fig. 22-16) and is one of the most abundant free amino acids in human tissues 455-457 Its concentration is high in excitable tissues, and it may be a neurotransmitter (Chapter 30). Taurine may have a special function in retinal photoreceptor cells. It is an essential dietary amino acid for cats, who may die of heart failure in its absence,458 and under some conditions for humans.459 In many marine invertebrates, teleosts, and amphibians taurine serves as a regulator of osmotic pressure, its concentration decreasing in fresh water and increasing in salt water. A similar role has been suggested for taurine in mammalian hearts. A chronically low concentration of Na+ leads to increased taurine.460 Taurine can be reduced to isethionic acid... 

The action of tyramine on nerve receptors is mainly indirect by release of norepinephrine and dopamine from neuronal storage sites (363, 384). Tyramine and its /3-oxidized counterpart octopamine have been referred to as false neurotransmitters because these compounds can be taken up, stored, and released from nerve endings in a way similar to those of the principal neurotransmitters norepinephrine and dopamine (385). Octopamine was first discovered in salivary glands of octopods (386). The compound is widely distributed in the animal kingdom and is present in high amounts in the nervous system of several species of invertebrates such as molluscs and arthropods, where it acts as a specific transmitter substance (387). Octopamine may also play a role in the regulation of adrenergic neurotransmission in mammals (387). Administration of octopamine to intact animals produces a transient rise in blood pressure (388). 

SAFETY PROFILE Poison by subcutaneous and intraperitoneal routes. Moderately toxic by ingestion. Questionable carcinogen with experimental neoplastigenic data. It mimics the action of acetylcholine, a neurotransmitter, and is a parasympathetic nervous system stimulant. Its action on the central nervous system can cause tremors. Human mutation data reported. It is easily nitrosated to several nitrosamines. See also ESTERS and NITROSAMINES. It is the major alkaloid found in betel quid. Combustible, can react with oxidizing materials. When heated to decomposition it emits highly toxic fumes of NOx. 

Electrochemical detection involves the induction of a change in redox state (electrolysis) by application of an electrical potential to an electrode (71). Compounds that can be readily detected by this means are termed electroactive. Under physiological conditions, these compounds tend to be in their reduced state in the nervous system because of the rich level of antioxidants (e.g., ascorbic acid) and, thus, can be oxidized by application of a positive potential to the electrode. The evolved electrons are detected at the electrode in the form of electrical current. This current is proportional to the number of electroactive molecules at the surface of the electrode, and therefore it is proportional to their concentration in the bulk solution. By implanting an electrode in the extracellular space close to the release site and detecting changes in the local (extracellular) concentration of the neurotransmitter, neurotransmitter release can be monitored. The key advantage of this approach is the high temporal resolution that can be in the millisecond domain. Neurotransmitters that can be detected this way include dopamine, norepinephrine, epinephrine, serotonin, and melatonin. 

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