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)

Recent studies have suggested that ethanol may exert some of its central depressant actions by increasing the extracellular levels of adenosine in the brain. Ethanol can inhibit the cellular uptake of adenosine, thus increasing its extracellular concentration. After ethanol metabolism by the liver, blood acetate levels are elevated and acetate metabolism in the brain could also lead to the production of adenosine. Rat cerebral cortical cup release experiments failed to reveal any elevation in the extracellular levels of either adenosine or inosine following the intraperitoneal (IP) administration of ethanol (1.5 g/kg) or acetate (2 g/kg). IP-administered ethanol (0.5 and 1.0 g/kg) enhanced the magnitude and duration of the inhibition by iontophoretically applied adenosine of the spontaneous firing of rat cerebrocortical neurons; an action which would be consistent with the block of adenosine uptake. Acetate, applied iontophoretically, depressed the spontaneous firing of 63% of the cerebrocortical neurons tested. 8-p-Sulphophenyltheophylline, an adenosine antagonist, was ineffective at blocking these inhibitions, indicating that adenosine generation is unlikely to have played a major role in the acetate-evoked depression of cerebral cortical neurons.
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PMID:Actions of ethanol and acetate on rat cortical neurons: ethanol/adenosine interactions. 147 11

Inhibition of tumor blood flow appears to a major antitumor mechanism of flavone acetic acid (FAA), although non-ischemic processes may also be a significant role. To distinguish between direct and immune effector cell-mediated cytotoxicity as the basis for non-ischemic killing, effects of FAA were compared in EMT6 spheroids grown entirely in vitro and spheroids recovered from the peritoneal cavities of mice after six days of in vivo growth (ex vivo spheroids). Approximately 50% of the cells in the latter case were of host origin (macrophages and lymphocytes). Ex vivo spheroids showed specific histological changes when exposed to FAA, including tumor cell rounding, apoptosis, depression of mitotic activity and dissolution of necrotic debris in the spheroid core. Quantitation of histological changes indicated these effects to be significantly greater in ex vivo than in vitro spheroids. The histological changes in FAA treated ex vivo spheroids were partially inhibited by dexamethasone. Oxygen tension did not influence the response of spheroids to FAA. The results suggest that immune effector cells, probably macrophages, mediate blood flow-independent antitumor effects of FAA.
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PMID:The role of immune effector cells in flavone acetic acid-induced injury to tumor cells in EMT6 spheroids. 148 17

Seasonal affective disorder is a form of depression which recurs at the same time of the year. Exposure to bright artificial light at a dose of 2,500 lux is used to treat seasonal affective disorders. We exposed a pigmented (Brown Norway) and a nonpigmented (Sprague-Dawley) rat strain with bright artificial light for 21 days at two doses (2,500 and 6,100 lux) and analyzed dopamine, dihydroxyphenyl-acetic acid, 5-hydroxytryptamine (5-HT), and 5-hydroxyindole-acetic acid (5-HIAA) by high performance liquid chromatography (HPLC) and electrochemical detection in eight different brain regions. Furthermore, we measured tissue levels of substance P (SP), neurokinins (NK), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) with radioimmunoassay. Our data obtained with light microscopy show that bright artificial light at both doses induced a massive destruction of photoreceptors in the retina of albino rats but not of the pigmented rat strain. Retinal lesion of photoreceptors resulted in increased tissue levels of all measured neuropeptides except SP in the hypothalamus and increased VIP in the ventral tegmental area/substantia nigra. Furthermore, increased 5-HT and 5-HIAA tissue levels were found in the ventral tegmental area/substantia nigra. In contrast, in the frontal cortex there was a significant reduction in 5-HIAA tissue levels and a decreased 5-HIAA/5-HT ratio, indicating decreased 5-HT metabolism. Light exposure of the pigmented rat strain revealed no changes in the measured biogenic amines and neuropeptides in any investigated brain region. Our data suggest that retinal lesion but not direct visual neurotransmission induced changes in neurotransmitters in some brain regions. We conclude that Brown Norway rats but not Sprague-Dawley rats are useful to study neurochemical effects of bright artificial light. However, Sprague-Dawley rats may be a useful tool to study biochemical mechanisms of photoreceptor damage by bright light.
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PMID:Effects of bright artificial light on monoamines and neuropeptides in eight different brain regions compared in a pigmented and nonpigmented rat strain. 152 5

The concentration of norepinephrine in the hippocampus of rats anesthetized with halothane (Wyeth-Ayerst, Philadelphia, Pa) is found to be markedly increased, presumably due to the stress of handling and administering the anesthetic. This increased norepinephrine concentration persists for about 50 minutes but is obliterated when the anesthetized rat is concussed. This 50-minute period corresponds to the time it takes for a rat (or human), comatose for 1-2 seconds following concussion, to regain normal memory. No changes in 3,4-dihydroxybenzene-acetic acid (DOPAC), 3-(3,4-dihydroxyphenyl) alanine (L-DOPA), and 3,4-dihydroxybenzylamine (DHBA) were noted. 5-Hydroxy indole acetic acid (HIAA) showed a depression at 5 minutes and again at 30 minutes, changes that were consistent but not considered statistically significant.
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PMID:Changes in hippocampal monoamine concentration following halothane anesthesia and concussion. 154 72

The intracerebroventricular (icv) administration of histamine but not N-telemethylhistamine and 1-methyl-4-imidazole acetic acid induced catalepsy in mice. Histamine H1-receptor blockers such as cyproheptadine, mepyramine and diphenhydramine reduced histamine-induced catalepsy. However, astemizole which is known to be without central effects, did not reduce histamine-induced catalepsy. The icv pretreatment with histamine H2-receptor blockers, such as metiamide and cimetidine, also had no effect. Moreover, various antidepressants, both imipramine- and atypical-type drugs antagonized histamine-induced catalepsy to various degrees in this experiment. Thus, the induction of catalepsy by icv administration of histamine was mediated through histamine H1-receptors, and suggested that antidepressants reduced histamine-induced catalepsy via this mechanism. Histamine-induced catalepsy is a possible new animal model of depression which can also be used for evaluation of atypical antidepressants.
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PMID:Effects of antidepressants and antihistaminics on catalepsy induced by intracerebroventricular administration of histamine in mice. 167 50

Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.
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PMID:The threshold of pain and neurotransmitter's change on pain in Parkinson's disease. 170 99

Day and nighttime melatonin production in the pineal gland was compared in normal and cardiomyopathic (polydystrophic) adult male Syrian hamsters. These strains of hamsters were selected for comparison because the cardiomyopathetic hamster displays a deficient transmembrane Ca(2+)-pump in a number of tissues, and intracellular CA2+ concentrations ([Ca2+]i) play a central role in the nocturnal increase in pineal melatonin synthesis. Daytime levels of all constituents measured, i.e., pineal N-acetyltransferase (NAT) activity, pineal and serum melatonin levels, and pineal 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) contents, were comparable in control and dystrophic hamsters. In contrast, the nighttime rises in pineal NAT activity and pineal and serum melatonin levels were significantly attenuated in the dystrophic hamsters. By comparison, the pineal contents of 5-HTP, serotonin, and 5-HIAA were essentially the same in both groups of hamsters with both pineal serotonin and 5-HIAA values exhibiting the usual nighttime drop. It is presumed that the alterations in nocturnal melatonin production in the pineal gland of the cardiomyopathic hamster may relate to a generalized deficiency in the Ca(2+)-pump in pinealocyte plasma membranes, which leads to unusually high [Ca2+]i, causing a depression of NAT activity; this leads to the commensurate decline in pineal and serum melatonin levels. Harderian gland NAT activity and melatonin levels were essentially similar in the two groups of animals, although NAT activity was slightly depressed in the dystrophic hamsters killed during the day. The reduced amounts of intrascapular brown fat in the cardiomyopathic hamster is speculated to be a result of the diminished amount of melatonin produced in these animals.
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PMID:Attenuated nocturnal rise in pineal and serum melatonin in a genetically cardiomyopathic Syrian hamster with a deficient calcium pump. 172 60

The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism.
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PMID:Comparison of gabapentin with other antiepileptic and GABAergic drugs. 186 22

The effects of levocabastine (R 50 547; CAS 79516-68-0) on the central nervous system were studied in comparison with those of diphenhydramine, ketotifen and azelastine. At high doses, levocabastine caused a decrease in locomotor activity, prolongation of thiopental-induced sleep, depression of acetic acid-induced writhing in mice and inhibition of active avoidance response in rats, but these adverse effects were much less potent than those seen in diphenhydramine, ketotifen and azelastine. Oxotremorine-induced tremor and salivation in mice were delayed after extremely high dosage of levocabastine; however, these were much less effective than those seen after diphenhydramine and ketotifen. Levocabastine did not affect the tonic extensor seizure induced by maximal electroshock in mice which is different from that of diphenhydramine. In EEG analysis, levocabastine at a dose of 20 mg/kg caused no significant changes in the EEG recorded from the frontal cortex, occipital cortex, hippocampus and amygdala in rats with chronic electrodes.
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PMID:Central effect of the potent long-acting H1-antihistamine levocabastine. 198 50

The analgesic and acute central nervous system (CNS) side effect potential of the enkephalinase inhibitor SCH 32615 (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenyl-alanine-beta-alanine) were evaluated after IV administration to mice, rats and squirrel monkeys. In mice, SCH 32615 caused dose-related suppression of acetic acid-induced writhing (minimal effective dose, MED = 3 mg/kg IV). In rats, SCH 32615 produced dose-related increases in the response latencies in the yeast inflamed-paw test (MED = 10 mg/kg IV). In squirrel monkeys, using a new hot-water bath tail-flick test, SCH 32615 significantly prolonged the escape latencies (MED = 100 mg/kg IV). These results in primates are the first data showing an analgesic action of an enkephalinase inhibitor in a reflex model of pain. When measured for its CNS side effect potential, SCH 32615 had no significant effects in rats (up to 100 times its analgesically active doses) or in monkeys (up to three times). In the mouse, at doses 100 times its minimal effective dose, SCH 32615 produced brief convulsions; these lasted only a minute, resolved quickly, and did not cause lethality. In contrast, in rats and squirrel monkeys, the standard opioid analgesic morphine produced profound CNS side effects; this was particularly notable in monkeys, in which morphine's maximal analgesic effects were associated with near lethal respiratory depression. These data demonstrate that SCH 32615 produces selective analgesic actions and that its acute side effect liability is less than that seen with a clinically used standard.
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PMID:Analgesic and acute central nervous system side effects of the intravenously administered enkephalinase inhibitor SCH 32615. 201 47


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