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Several studies have shown the presence of melatonin and related compounds in grapes and wines. The latter provides evidence of the possibility to enhance the nutraceutical properties of premium wines. However, there are many external factors that can influence the levels of this indolamine in grape and wines. In this study, the monitoring of melatonin and its tentatively identified isomer was carried out during the entire winemaking process in Vitis vinifera cv. Malbec by ultra high-performance liquid chromatography-tandem mass spectrometry. Laboratory and pilot studies were carried out to elucidate the role of grape, yeasts, and tryptophan in the evolution of the indolamines during the fermentation process. Melatonin was detected in grape extract within the range 120-160 ng/g while its isomer was found in musts and finished wines. Our results demonstrate that Saccaromyces cervisiae plays a decisive role in contributing to the content of melatonin and its isomer in wine.

A facile and efficient one-pot three-component synthesis of spiroazepinoindolones has been developed. Using DMF as solvent without any additional acid or metal catalysts, the three-component reaction of readily available isatins, indolamines, and Meldrum's acid affords a new class of spiroheterocycles in moderate yield.

In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.

Migraine is a paroxysmal disorder characterized by recurrent attacks of headache, with or without associated visual and gastrointestinal disturbances. Migraine can be classified in two main groups, common and classic. Theories trying to explain the pathogenesis of a migraine attack may emphasize either the central or peripheral aspects of the disease. The vascular theory may stress the importance of either central or peripheral blood flow or both. Cerebral vasoconstriction in the early phases of the attack is followed by vasodilatation and pain. Biochemical mediators of vascular responses are not exactly known, but platelets and 5-hydroxytryptamine and thromboxane released from them as well as noradrenaline are potent vasoconstrictors, while kinins and prostaglandins can explain the vasodilatory phase of migraine attacks. This review presents evidence for the role of arachidonic acid metabolites, prostaglandins and leukotrienes in migraine. The evidence comes from the measurements of eicosanoids in biological fluids during and after the attack, infusion studies where vasodilatory prostaglandins mimic the migraneous symptoms, and the good effect of non-steroidal anti-inflammatory drugs in the treatment and prophylaxis of migraine attacks. Additional data are based on experimental biochemical studies in which catecholamines and indolamines have been shown to increase the synthesis of vasodilatory prostaglandins. However, the final evidence still awaits its confirmation.

Neurofibrillary tangles and amyloid plaques express acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in Alzheimer's disease. We had found that traditional AChE inhibitors such as BW284C51, tacrine and physostigmine were more potent inhibitors of the AChE in normal axons and cell bodies than of the AChE in plaques and tangles. We now report that the reverse pattern is seen with indolamines, carboxypeptidase inhibitor, and the nonspecific protease inhibitor bacitracin. These substances are more potent inhibitors of the cholinesterases in plaques and tangles than of those in normal axons and cell bodies. These results show that the enzymatic properties of plaque and tangle-associated cholinesterases diverge from those of normal axons and cell bodies. The selective susceptibility to bacitracin and carboxypeptidase inhibitor indicates that the catalytic sites of plaque and tangle-bound cholinesterases are more closely associated with peptidase or protease-like properties than the catalytic sites of cholinesterases in normal neurons and axons. This shift in enzymatic affinity may lead to the abnormal protein processing which is thought to play a major role in the pathogenesis of AD. The availability of pharmacological and dietary means for altering brain indolamines raises novel therapeutic possibilities for inhibiting the abnormal cholinesterase activity associated with Alzheimer's disease.

The study of cerebral ischemia in animals is not easy, because cerebral circulation is not the same as in humans. Indeed, in most animals, there is a collateral circulation between the vertebral and carotid arteries before these arteries enter the brain. On the other hand, in gerbils, unilateral ligation produces ischemia in the ipsilateral forebrain and leads to death in 40–60% of the animals. Because the cerebral ischemia so produced is not effective in all gerbils, it is important to select “sensitive” gerbils by funduscopic examination. Only sensitive gerbils are retained for further experimentation. The nature of the aging process is the subject of some speculation. One hypothesis is referred to as the free radical theory. This theory postulates that free radicals are involved in aging and age-related disorders of the brain. Therefore, we have determined levels of neuromediators involved in cerebral ischemia and memory, including catecholamines (dopamine [DA], dihydroxyphenylacetic acid [DOPAC], hydroxyvanillic acid [HVA]) and indolamines (5-hydroxyindolacetic acid [5HIAA], serotonin [5-HT]), amino acids (aspartate, glutamate and GABA), and free radicals (.OH). We have chosen for study the caudate nucleus, hippocampus, and retina, where changes after ischemia/reperfusion insult are well documented. In gerbil brain, levels of .OH and neurotransmitters are low at birth, reach a plateau, and then decrease with aging. After cerebral ischemia (60 min) induced by left carotid occlusion, the reperfusion (30 min) symptoms are classified using a behavioral score (Stroke Index). Moreover, after ischemia/reperfusion insult (IRI), increases in Stroke Index, .OH, glutamate, aspartate, GABA, monoamines, and indolamines are more pronounced in older gerbils. © 1992 Wiley-Liss, Inc.

As 5 alpha-reductase is involved in the metabolism of indolamines in the Harderian glands of Syrian hamsters, we have compared the effects of androgen deprivation and the administration of the potent 5 alpha-reductase inhibitor N,N-diethyl-4-methoxy-3-oxo-4-aza-5-androstene-17-carboxamida on Harderian porphyrin metabolism. Ten days after castration, porphyrin levels had increased to 40 times the values of intact hamsters. However, the inhibition of 5 alpha-reductase, which resulted in a significant decrease in the weight of accessory sex glands, did not modify porphyrin concentrations within the Harderian glands. It is concluded that, contrary to the situation for indolamine metabolism, testosterone per se is the main androgen involved in the sexual differences observed in Harderian porphyrin metabolism.

Drosophila melanogaster homogenates incubated with tritiated 5-hydroxytryptophan, 5-hydroxytryptamine, or N-acetylserotonin have the ability of converting them into labelled indolamines, including melatonin. All these compounds were characterized by two-dimensional thin-layer chromatography by comparison with nonradiolabelled standards, and melatonin by mass spectrometry and radioimmunoassay. On the other hand, the injection of pharmacological doses of melatonin into 2-day-old female flies diminishes the mating speed and the oviposition rate.

The rhythmical activity of the liver fluke, Fasciola hepatica, was stimulated by 5-hydroxytryptamine and by lysergic acid diethylamide at very low concentrations. The effect was peripheral and was not mediated through the central ganglion. Other amines also stimulated rhythmical activity, the most potent being the indolamines. Bromolysergic acid diethylamide, and other analogues such as yohimbine, harmine, and dopamine depressed rhythmical movement and antagonized the stimulant action of 5-hydroxytryptamine and lysergic acid diethylamide. Evidence which suggests the presence of tryptamine receptors in the trematode is discussed.