5 -hydroxytryptamine

5-Hydroxytryptamine may itself undergo conjugation. Substances closely related to it, e.g., Erspamer s enteramine I, have been reported in several cases (e.g., 179, and review 237). 

W-Methylated derivatives may also be formed in mammals (113a). 

Wieland and co-workers (913) in 1931 isolated from the skin secretion of the toad two indole derivatives, bufotenin and bufotenidin, whose correct structure (diagram 24) was established soon after (914) and confirmed by synthesis (416, cf. 363). Dehydrobufotenin was isolated in 1935 (443) and the previously isolated bufothionin (915) shown to be its sulfate ester (916, cf. diagram 24). 

These substances are fairly widely distributed amongst amphibia (197, 444, review 196) and have a powerful physiological action (e.g., 233,235). Their occurrence and pharmacology have been extensively studied by Er- 

Diagram 24. M ethylation products of enteramine (5-hydroxytryptamine) occurring especially in amphibia. 

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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. 

Other studies indicate that sucrose does not cause hyperactivity. Carbohydrate ingestion increases levels of serotonin (5-hydroxytryptamine), a brain neurotransmitter that promotes relaxation and sleep. Dietary sucrose should theoretically have a calming effect and reduce activity, manifestations which have been observed in case studies (63). To date, clinical investigations have failed to show a significant connection between sucrose consumption and aggressive or dismptive behavior (66). 

The surface of the green coffee contains a cuticular wax layer (0.2—0.3% db) for both varieties. The wax contains insoluble hydroxytryptamides derived from 5-hydroxytryptamine [61 7-2] and saturated C18—C22 fatty acids. 

Angiotensinogen (from human blood serum) [643I5-I6-8]. Purified by chromatography on Blue Sepharose, Phenyl-Sepharose, hydroxylapatite and immobilised 5-hydroxytryptamine [Campbell et al. Biochem J 243 121 1987]. 

Evidence has been put forward that 6-methoxy-l-methyl-l,2,3,4-tetrahydro-j3-carboline may be a component of animal tissues and may be identical with adrenoglomerulotrophine, a factor controlling aldosterone secretion, which is found in the pineal gland where it occurs together with 5-hydroxytryptamine... 

It has been suggested that the blue-green fluoreseenee produeed when 5-hydroxytryptamine is treated with ninhydrin is due to the formation of jS-earboline derivatives and that a brilliant orange-red... 

The involvement of serotonin (5-hydroxytryptamine) in disease states has been recognized for several decades. Research on antagonists awaited the recent development of methodology involving serotonin receptors. A thiazolopyrimidone serves as the nucleus for a pair of serotonin antagonists. The key intermediate 118 is in fact simply the lactonized form of 2-hydroxyethyl acetoace-tate. Condensation of this P-keto ester can be visualized to involve initial attack on the reactive... 

B.-M. Eriksson and B.-A. Persson, Determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in plasma by direct injection in coupled-column liquid clrromatography with electrochemical detection , 7. Chromatogr. 459 351-360 (1988). 

Dopa decarboxylase is an enzyme catalyzing the synthesis of dopamine from l-DOPA or of serotonin (= 5-hydroxytryptamine) from L-tryptophan. Inhibitors of this enzyme, which do not pass through the... 

Serotonin or 5-hydroxytryptamine is an important biogenic amine, which is synthesized via 5-hydroxy-tryptophan from the amino acid tryptophan. The highest concentration of serotonin occurs in the wall of the intestine. About 90% of the total amount is present in enterochromaffrn cells, which are derived from the neural crest, similarly to those of the adrenal medulla. 

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)... 

Hoyer D, Clarke DE, Fozard JR et al (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46 157-204... 

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... 

Anand M, Gopal K, Agrawal C, et al. 1986. Endosulfan induced inhibition of 3H 5-hydroxytryptamine uptake in platelets. Toxicol Lett 32 203-208. 

Hydroxytryptamine 380 5-Hydroxytryptophan 240,241 Hydroxytyramine 392 Hyodesoxycholic acid 334 Hyperici, Extract. 279 Hypericin 148, 279, 280 Hyperoside 149,279,323 -, -quercetin 280... 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

There is 5-hydroxytryptamine in weever fish venom besides protein. It is believed that local pain is attributed to the presence of 5-hydroxytryptamine (27). Other small compounds such as histamine, adrenaline, and noradrenaline are also present in the weever fish (28). 

Some derivatives of adamantane with antagonist or agonist effects have also been synthesized. For instance, monocationic and dicationic adamantane derivatives block the a-amino-3-hydroxy-5-methylisoxazole -propionic acid (AMPA) receptors, A-methyl-o-aspartate (NMDA) receptors [134—136] and 5-hydroxytryptamine (5-HT3) receptors [137]. 

HT3 receptor. 5-Hydroxytryptamine receptor a receptor for serotonin (a neurotransmitter), which activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

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