Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical efficacy of lithium augmentation in refractory depression is hypothesized to depend on the ability of lithium to enhance presynaptic 5-hydroxytryptamine (5-HT) function. Since fenfluramine promotes release and inhibits reuptake of presynaptic 5-HT, we assessed its efficacy in augmenting ongoing tricyclic antidepressant treatment of refractory depression. Fifteen patients with DSM-III major depression failed to respond to treatment with desipramine 2.5 mg/kg/day or more (plasma levels of at least 125 ng/ml) given for at least 4 weeks. Fenfluramine 40-120 mg/day was then added to the ongoing desipramine in a placebo substitution design. There was no statistically significant evidence of either transient or sustained clinical improvement during the 2 weeks of fenfluramine augmentation. One patient appeared to respond to the treatment, but one appeared to worsen. Fenfluramine more than doubled steady-state plasma levels of desipramine. These findings suggest that lithium's efficacy as an augmenting agent depends on properties that are not shared by fenfluramine. Fenfluramine cannot be recommended in the routine management of refractory depression.
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PMID:Fenfluramine augmentation in tricyclic-refractory depression. 225 48

5-hydroxytryptamine (5-HT) was delivered microiontophoretically (20-80 nA) to cells of the lateral vestibular nucleus of anaesthetized rats to test its influence on the spontaneous activity of single neurons. 5-HT increased the rate of firing of 94% of the units tested. The enhancement persisted for up to 700 s after the end of the 5-HT ejection and the maximum magnitude of the excitation (10-3400%) showed a hyperbolic correlation (rho = 0.86) with background firing. In 43% of units the enhancement was preceded by a short-lasting (less than 105 s) depression of the neuronal firing rate, the magnitude of which was unrelated to the background mean firing rate. Both components of the 5-HT response were dose-dependent. Only the excitatory responses were antagonized by metergoline, methysergide and ketanserin. The putative 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine, applied microiontophoretically, depressed the background firing rate and was not antagonized by methysergide. These results demonstrate that 5-HT modifies the responsiveness of vestibular neurons and suggest that at least two mechanisms and maybe two types of receptors are activated by 5-HT in this nucleus.
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PMID:Effects of 5-hydroxytryptamine on the firing rates of neurons of the lateral vestibular nucleus in the rat. 232 76

Fluoxetine (Prozac) is a nontricyclic serotonin (5-hydroxytryptamine) reuptake inhibitor commonly prescribed for the treatment of depression. Fluoxetine also blocks 5-hydroxytryptamine reuptake in platelets and could potentially lead to clinically significant platelet dysfunction. We describe a patient who developed petechiae and prolongation of the bleeding time while receiving fluoxetine therapy.
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PMID:Fluoxetine and the bleeding time. 236 31

Aging was associated with an increase in the density of specific binding sites for [3H]imipramine in postmortem specimens of human hypothalamus, frontal cortex, and parietal cortex. In general, [3H]imipramine binding was not affected by factors considered difficult to control in postmortem studies, i.e., time from death to autopsy and cause of death. The in vitro regulation of [3H]imipramine binding by sodium was impaired with age in hypothalamic homogenates. In vitro regulation of [3H]imipramine binding by chloride was intact. Determination of the concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid in hypothalamus and frontal cortex indicated no apparent age-related changes in indole metabolism. The age-related increase in brain [3H]imipramine binding and impairment in the in vitro regulation of binding by ions are similar to changes observed previously in aged mouse brain. The increase in brain antidepressant binding sites is discussed in relationship to other indices of brain serotonergic function in aging and to the relationship of [3H]imipramine binding and depression.
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PMID:Elevated density of [3H]imipramine binding in aged human brain. 241 70

A topographic map of the substance P and monoamine neurons in the ventrolateral medulla of the cat has been constructed from peroxidase anti-peroxidase immunohistochemically stained sections. The coordinates of this map use the foramen cecum of the medulla oblongata (i.e. the triangular depression at the junction between the caudal boundary of the pons and the rostral limit of the median fissure between the pyramidal tracts) as the zero point. Two distinct groups of substance P neurons have been found: a rostral group lies ventral to the facial nucleus and a caudal one is found ventrolateral to the inferior olivary nucleus. Two dopamine beta-hydroxylase-containing cell groups were identified that correspond to the A1 and A5 cell groups. The A5 cell group lies dorsal, lateral and caudal to superior olivary nucleus. The A1 cell group lies approximately 4.0-5.0 mm lateral to the midline at the level of the inferior olive; these cells lie mainly dorsolateral to the region of the magnocellular division of the lateral reticular nucleus. The B1 and B3 serotonin (5-hydroxytryptamine) cell groups of the ventrolateral medulla appear to form a continuous column with a rostral and a caudal swelling. The rostral group begins at the level of the facial nucleus (approximately 4 mm caudal to the foramen cecum) and is concentrated in the area just lateral to the pyramidal tract. It becomes reduced in size approximately 8.0 mm caudal to the foramen cecum, and then enlarges to form a caudal group (approximately 10 mm caudal to foramen cecum). Portions of this column overlap with the caudal substance P cell group. The C1 cell group lies in a restricted zone approximately 4.0 mm lateral to the midline at the level of the rostral part of the inferior olivary nucleus.
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PMID:Topographic organization of substance P and monoamine cells in the ventral medulla of the cat. 241 70

Serotonergic mechanisms have been investigated in postmortem brain samples from controls and suicide victims. The concentrations of 5-hydroxytryptamine (serotonin; 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in occipital cortex and hippocampus and the high-affinity binding of ligands to the 5-HT1, 5-HT2 and imipramine-binding sites was assessed in frontal cortex, occipital cortex and hippocampus. The only significant difference between the two groups was a modest increase in 5-HIAA levels in the hippocampus of suicide victims. There was no evidence to suggest that those suicide victims with a clinical history of depression represented a subgroup with altered metabolite levels or binding values. The storage conditions of the samples were not related to the metabolite levels or binding values. There was, however, a significant positive correlation between [3H]imipramine binding and age in some brain regions. The results do not provide any evidence of gross alterations in 5-HT mechanisms in suicide or depression.
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PMID:Serotonergic mechanisms in brains of suicide victims. 241 65

The responsiveness of functionally identified cat spinal dorsal horn neurons to iontophoretically applied substance P (SP) and 5-hydroxytryptamine (5-HT) has been investigated by means of extracellular recording after 5-HT depletion with p-chlorophenylalanine (p-CPA). In addition, the spinal levels of 5-HT, SP, cholecystokinin octapeptide, neurotensin, and vasoactive intestinal polypeptide have been measured in intact and p-CPA-pretreated cats. In the present study we have demonstrated an altered responsiveness of dorsal horn neurons to locally applied SP and 5-HT. We found in p-CPA-pretreated cats that the proportion of neurons responding with excitation to SP and 5-HT was significantly increased. At the same time, depression induced by 5-HT in the dorsal horn cells was virtually absent in p-CPA-pretreated animals. Our finding that spinal level of 5-HT was significantly decreased in p-CPA-treated animals is consistent with previous studies. No convincing alteration in the spinal levels of 4 analyzed peptides was found in p-CPA-treated animals. The present study has shown that pharmacological depletion of 5-HT has two major effects: (1) it increases significantly the proportion of dorsal horn neurons excited by SP and 5-HT; and (2) it is ineffective in inducing 5-HT supersensitivity. Further work is needed to explain mechanisms involved in these effects.
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PMID:Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine. 242 Apr 13

3,7-Dihydro-7-[2-hydroxy-3-[4-[3-(phenylthio) propyl]-1-piperazinyl]propyl]-1,3-dimethyl-1H-purine-2,6-dione dihydrochloride (tazifylline, RS-49014) potently inhibited contractions evoked by stimulation of histamine H1-receptors in isolated guinea pig ilea and exhibited high affinity for these receptors in radioligand binding studies in vitro. In rats, guinea pigs and dogs the antihistaminic effect of tazifylline was rapid in onset and long-lived. In anesthetized guinea pigs, tazifylline markedly inhibited histamine-induced bronchoconstriction and protected conscious animals from the lethal effect of large doses of the amine. In conscious rats, tazifylline was more potent in reducing the inflammatory effects of intradermal histamine than that evoked by anaphylactic reaction. In conscious dogs, orally administered tazifylline inhibited histamine-induced skin inflammation for long periods of time and in anesthetized animals attenuated that portion of the histamine-evoked hypotension attributable to stimulation of H1-receptors. Results obtained from a variety of in vitro and in vivo experimental preparations showed that tazifylline had much lower affinity for histamine H2-receptors, alpha- and beta-adrenoceptors, 5-hydroxytryptamine and muscarinic receptor subtypes. Tazifylline poorly inhibited the release of histamine from rat peritoneal mast cells. Large oral doses of tazifylline did not reduce spontaneous locomotor activity in mice, nor did they produce overt symptoms of behavioral depression in conscious rats. Therefore, tazifylline is a potent, selective and long-acting histamine H1-receptor antagonist that does not appear to produce central depression in animals.
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PMID:Animal pharmacology of the selective histamine H1-receptor antagonist tazifylline. 242 63

Male rats (100 g) previously adapted to a 20% casein diet were fed diets containing from 0 to 55% of casein and were killed after 20, 60, 150, 240, or 330 min. Food intake of rats fed a protein-free diet or a diet containing greater than 35% of casein was depressed within 20 min and remained depressed for up to 5.5 h. Depressed food intake of rats fed protein-free diets was accompanied by a rapid reduction in plasma and brain total concentrations of free indispensable amino acids (IAA). Food intake depression among groups fed diets containing in excess of 35% casein was associated with elevated plasma and brain total IAA concentrations, compared with those of animals fed diets containing 15-20% of casein. No consistent relationships were observed between food or protein intakes and whole-brain concentrations of 5-hydroxytryptamine, 5-hydroxyindole-3-acetic acid, or their sum. Our results suggest that in animals fed a single diet, food intake is depressed if the total concentration of free IAA in brain either falls below a certain critical minimum or exceeds some maximum tolerable level.
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PMID:Acute effects of dietary protein on food intake, tissue amino acids, and brain serotonin. 243 9

The response of brain dopaminergic and serotonergic systems to the amphetamine-like designer drugs, 3,4-methylenedioxyamp amphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), was investigated and compared to methamphetamine (METH). Like METH, single or multiple doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) in several brain regions. The reduction in 5HT content corresponded to the depression of TPH activity in all regions examined. In contrast to METH, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
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PMID:The effects of amphetamine-like designer drugs on monoaminergic systems in rat brain. 244 19


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