Hydroxytryptamine 5-HT

The 5-HT3 antagonists ondansetron (Zofran) and granisetfon (Kyttil) are effective in relieving the nausea and vomiting that are side-effects of radiotherapy and treatment with cytotoxic drugs. They probably function by a combination of central and peripheral actions. 

Alosetron (Lotfonex) is effective in certain variants of irritable bowel syndrome (IBS), but was withdrawn from use because it may cause serious side-effects. However, it was later re-instated for restficted use following petitions from patients. 

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Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

Serotoninergic System. Figure 1 Graphical representation of the current classification of 5-hydroxytryptamine (5-HT) receptors. Receptor subtypes represented by shaded boxes and lowercase designate receptors that have not been demonstrated to definitively function in native systems. Abbreviations 3-5r cyclic adenosine monophosphate (cAMP) phospholipase C (PLC) negative (-ve) positive (+ve)... 

Tryptamine itself is found in all major centers of the brain. Its physiologic role in central nervous system (CNS) function, however, remains unclear. 5-Hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter in the CNS. The structural similarity of the tryptamine-related hallucinogens with 5-HT presumably forms the neurochemical basis for their action within the CNS. 

Schreiber R, Brocco M, Audinot V, et al (l-(2,5-Dimethoxy-4 iodophenyl)-2-amino-propane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors modulation by novel 5-HT2A/2C antagonists, Dj antagonists and 5-HTagonists. J Pharmacol Exp Ther 273 101—112, 1995 Screaton GR, Singer M, Cairns HS, et al Hyperpyrexia and rhabdomyolysis after MDMA ( ecstasy ) abuse. Lancet 399 667—668, 1992... 

A link between the central monoamines, 5-hydroxytryptamine (5-HT) and noradrenaline, and depression was forged some 40 years ago and arose from clinical experience with the drugs, reserpine and iproniazid. At that time, reserpine was used as an... 

The problem of selectivity is the most serious drawback to in vivo electrochemical analysis. Many compounds of neurochemical interest oxidize at very similar potentials. While this problem can be overcome somewhat by use of differential waveforms (see Sect. 3.2), many important compounds cannot be resolvai voltammetrically. It is generally not possible to distinguish between dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) or l tween 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA). Of even more serious concern, ascorbic acid oxidizes at the same potential as dopamine and uric acid oxidizes at the same potential as 5-HT, both of these interferences are present in millimolar concentrations... 

Racke, K., Schworer, H., Simson, G. Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and non-smokers. Clin. Invest. 70 201, 1992. 

Neurochemical theories for the affective disorders propose that there is a link between dysfunctional monoaminergic synapses within the central nervous system (CNS) and mood problems. The original focus was the neurotransmitter noradrenaline, or NA (note noradrenaline is called norepinephrine, or NE, in American texts). Schildkraut (1965) suggested that depression was associated with an absolute or relative deficiency of NA, while mania was associated with a functional excess of NA. Subsequently, another monoamine neurotransmitter 5-hydroxytryptamine (5-HT), or serotonin, was put forward in a rival indoleamine theory (Chapter 2). However, it was soon recognised that both proposals could be reconciled with the available clinical biochemical and pharmacological evidence (Luchins, 1976 Green and Costain, 1979). 

Nowhere is the need for specificity so great as in trying to design therapies for the human brain. Here there are numerous receptors that affect our moods, sleep, alertness, memory, and coordination. Even though the importance of serotonin (5-hydroxytryptamine, 5-HT) had been known to neuroscientists for over 100 years, it wasn t until the discovery of drugs... 

Sensitive electrochemical techniques have also been developed to directly measure the release of oxidizable neurotransmitters such as catecholamines (CAs) and serotonin (5-hydroxytryptamine, 5-HT). Current flows in the circuit when the potential of the electrode is positive enough to withdraw electrons from, i.e. oxidize, the released neurotransmitter. The technique is very sensitive and readily detects the release of individual quanta of neuro transmitter resulting from the fusion of single secretory vesicles to the plasmalemma (Fig. 10-2). 

FIGURE 13-1 Chemical structure of 5-hydroxytryptamine (5-HT serotonin) and related indolealkylamines. The indole ring structure consists of the benzene ring and the attached five-member ring containing nitrogen. 

Bonaventure, P., Nepomuceno, D., Kwok, A. et al. Reconsideration of 5-hydroxytryptamine (5-HT)7 receptor distribution using [3H]5-carboxamidotryptamine and [3H]8-hydroxy-2-(di-n-propylamino)tatraline Analysis in brain of 5-HT 1A knock-out and 5-HT1A,1B double knock-out mice. /. Pharmacol. Exp. Ther. 302 240-248, 2002. 

Serotonin Binds to 5-hydroxytryptamine (5-HT) receptor to act as excitatory and inhibitory neurotransmitter in its inhibitory function, it can treat anxiety and depression in its excitatory function, it is an antipsychotic. 

Biogenic amines are of great interest to researchers because of their potential roles in several psychiatric and neurological disorders. They include dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT, serotonin), histamine, and trace amines such as 2-phenylethylamine (PEA), tyramine, octopamine, phenylethanolamine, and tryptamine (Coutts and Baker, 1982). Although GC assays for DA, NA, and 5-HT are available, HPLC analysis with electrochemical detection has for many years now been the method of choice for analysis of these neurotransmitter amines. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

Another proposed mechanism of byssinosis is pharmacologic mediator release, especially histamine and 5-hydroxytryptamine (5-HT). Studies of histamine release following cotton dust exposure are complicated by the fact that cotton Itself contains histamine (98), the majority of which is found in the dust particle fraction below 20 P size (99). 

In a series of studies, Markou and her colleagues have sought to identify drugs that ameliorate the changes in brain reward function evoked by nicotine withdrawal (see Kenny and Markon 2001 for review). This review snmmarises the evidence that 5-hydroxytryptamine (5-HT) and, especially, 5-HTia receptors may play an important role in nicotine withdrawal, although the specific nature of the changes evoked... 

Tryptophan possesses a complex heterocyclic side chain known as indole. It is the metabolic precnrsor to serotonin (5-hydroxytryptamine 5-HT), an important nenrotransmitter. 

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

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