Neurotransmitters such as Dopamine

Trace amines are a family of endogenous monoamine compounds including (3-phenylethylamine (PEA), p-tyramine (TYR), tryptamine (TRP) and octopamine (OCT). The trace amines share close structural similarity with the well known classical monoamine neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-HT). As their name suggests, trace amines occur in comparably much lower abundance than monoamine neurotransmitters. For historical reasons, other endogenous amine compounds which might share some structural similarities with PEA, TYR, TRP or OCT are not referred to as trace amines. 

Progesterone produces direct membrane effects [16]. These include actions that promote maturation of spermatozoa as well as oocytes and facilitation of the release of neurotransmitters such as dopamine and LH-releasing hormone (LHRH) (Fig. 52-7). Membrane actions of progesterone also activate oxytocin receptors in the hypothalamus in a way that enables oxytocin to turn on sexual behavior in the estrogen-primed female rat [3],... 

The pathology of Parkinson s disease is associated with a substantial reduction in neurotransmitters such as dopamine, 5-hydroxytryptamine, GABA, in the brain. Treatment is based on the use of replacement of dopamine or dopamine agonists which relieve the rigidity but do not affect a cure. Currently, there is no laboratory-based diagnostic test for PD and so diagnosis is based on clinical presentation alone. 

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

Deficiency of this coenzyme can lead to many manifestations. Clinical signs include retarded growth, acrodynia, alopecia, skeletal changes and anemia, while changes in neurotransmitters, such as dopamine, serotonin, norepinephrine (noradrenaline), tryptamine, tyramine, histamine, y-aminobutyric acid, and taurine, affect the brain function and can lead to seizures and convulsions. An overdose of vitamin Bg leads to neuronal damage and sensory and motor effects [417],... 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

Drugs that enhance GI motility are often called prokinetics. Their goal is to increase contractile force and accelerate intraluminal transit. Most of these drugs act either by enhancing the effect of acetylcholine or by blocking the effect of an inhibitory neurotransmitter such as dopamine. The prokinetics discussed in this chapter are metoclopramide, cisapride and tegaserod, and erythromycin. 

Monoamine oxidases (MAOs) are involved in the metabohsm of catecholamine and serotonin neurotransmitters such as dopamine, norepinephrine, and epinephrine. 

Tacrine has been found to be somewhat effective in patients with mild-to-moderate symptoms of this disease for improvement of cognitive functions. The drug is primarily a reversible cholinesterase inhibitor that increases the concentration of functional ACh in the brain. However, the pharmacology of tacrine is complex the drug also acts as a muscarinic receptor modulator in that it has partial agonistic activity, as well as weak antagonistic activity on muscarinic receptors in the CNS. In addition, tacrine appears to enhance the release of ACh from cholinergic nerves, and it may alter the concentrations of other neurotransmitters such as dopamine and NE. 

Receptors are proteins usually embedded in the cell s membrane. A neurotransmitter such as dopamine docks at its receptor, activating it and initiating some kind of response in the postsynaptic cell. The response depends on the type of receptor, and there are a number of different ones for most neurotransmitters. Researchers have found five dopamine receptors the one affected by chlorpromazine and similar drugs is known as D. These drugs prevent dopamine from activating the receptor. 

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... 

We have already noted that potentized Agaricus muscarius influences catalepsy in mice. It is known that neurotransmitters such as dopamine and serotonin... 

Flavin-containing mitochondrial MAO-A and MAO-B catalyze the oxidative deamination of neurotransmitters, such as dopamine, serotonin, and norepinephrine in the central nervous system and peripheral tissues. The enzymes share 73% sequence homology and follow the same kinetic and chemical mechanism but have different substrate and inhibitor specificities. Chemical modification experiments provide evidence that a histidine residue is essential for the catalysis. There is also strong evidence that two cysteine residues are present in the active site of MAO. 

Depression has been noted in 10 to 15% of all patients who take reserpine for the treatment of hypertension. When used for the treatment of tuberculosis, isoniazid brings about mood elevation. Reserpine was found to diminish the levels of brain neurotransmitters such as dopamine, serotonin, and norepinephrine, whereas isoniazid, through its monoamine oxidase inhibitory actions, augments the levels of these substances. It was thus theorized that too much of one or more of these neurotransmitters might be associated with states of hypomania or mania, whereas too little would correlate with depression. 

Fiber electrodes -> microelectrodes in a form of bare fibers as the conductive elements, protruding from the end of an insulator, usually made of carbon fibers of 7-8 pm diameter and sealed in glass capillaries often used for direct measurements (e.g., using fast cyclic voltammetry) of the in-vivo release of oxidiz-able neurotransmitters, such as dopamine, serotonin, norepinephrine, or epinephrine, from living cells. Also used to monitor electric activity of single nerve cells or for diagnostic purposes in electroanalysis. S ee also carbon fiber electrode. 

Current concepts of how and why neurotransmitter dysfunction may contribute to schizophrenia stem from decades of experience with modulatory neurotransmitters such as dopamine or serotonin. However, there are several major differences involved in viewing schizophrenia from a glutamatergic, rather than a dopaminergic, perspective. 

The enzyme catechol-O-methyltransferase (COMT) is involved in pain regulation and regulation of neurotransmitters. COMT acts to catalyze the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM, 5) to the 0 of catecholate 4 (Reaction 9.5). The catechol structure is found in neurotransmitters such as dopamine, noradrenahne, and adrenaline. A related set of enzymes are the DNA methyltransferases that appear to have similar structure, especially in their active sites, to the structure of COMT. ... 

Greg Gerhardt pioneered a chronoamperometry method that has been used to observe diffusion and uptake parameters in the rat brain (45). In this technique an exogenous neurotransmitter, such as dopamine, is introduced into the brain by pressure ejection or iontophoresis. The microelectrode is a known distance from the ejection pipette, so the analyte concentration detected at the microelectrode is a function of extracellular diffusion and uptake by the dopamine transporter. Because an exogenous neurotransmitter is introduced, the analyte being detected is known, and selectivity is not a problem. After a dopamine... 

Monoamine oxidases (MAO-A and MAO-B) are mitochondrial enzymes that oxidatively deaminate endogenous biogenic amine neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine. MAOs are like EMOs in that they catalyze the oxidation of drugs to produce drug metabolites that are identical in chemical structures to those formed by CYPs. Because the resulting structures are... 

Neuro transmitter hypothesis Apart from a disorder of the postsynaptic receptors, discussion centres on (1.) formation of false neurotransmitters such as octopamine and phenylethanolamine due to the accumulation of phenylalanine and tyrosine, (2.) decrease in excitatory neurotransmitters such as dopamine and noradrenaline, and (3.) increase in inhibitory neurotransmitters, such as GABA and serotonin. 

As low concentrations of dopamine are released and rapidly cleared from the extracellular space, the sensing electrodes must be sensitive, and selective and respond quickly[6]. For in vivo detection of neurotransmitters such as dopamine, physically small electrodes are advantageous due to their small size and high sensitivity to catecholamines[34]. There are currently no electrodes small enough to measure dopamine concentrations within the approximately 100-nm synapse, but considerable developments are being made in minimizing electrode size to approach synapses as closely as possible and also to minimize... 

These include the effects of nerve agents on y-amino-butyric acid neurons and cyclic nucleotides. In addition, changes in brain neurotransmitters, such as dopamine, serotonin, noradrenaline, as well as acetylcholine, following inhibition of brain cholinesterase activity, have been reported. These changes may be due in part to a compensatory mechanism in response to overstimulation of the cholinergic system or could result from direct action of nerve agent on the enzymes responsible for noncholinergic neurotransmission. 

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