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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.
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PMID:Interaction of biogenic amines with ethanol. 23 68

Volunteers inhaled a constant concentration of 50 ppm trichloroethylene (Tri) for 6 hrs per day on 5 consecutive days. Simultaneous ethanol (EtOH) ingestion (blood level 0.6%) inhibits the metabolization of Tri to trichloroethanol (TCE) and trichloroacetic acid (TCA) by 40% on the average. Oxidation of Tri to TCA does not occur as long as EtOH is present. During this time period the blood Tri-concentration increases 2 1/2-fold, that in the expired air rising 4-fold, as compared to Tri inhalation without EtOH. TCE glucuronidation is not subject to inhibition. On concurrent inhalation of Tri, the EtOH and acetaldehyde levels are slightly increased over the control values without Tri. The mechanisms underlying the alternate inhibition of mixed-function oxygenases and aldehyde dehydrogenase on simultaneous intake of Tri and EtOH are discussed. The intolerance reaction occurring on combined exposure to Tri and EtOH can be interpreted as an accumulation of Tri in the CNS resulting from the complete depression of Tri oxidation.
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PMID:Metabolism of trichloroethylene in man. III. Interaction of trichloroethylene and ethanol. 117 50

Administration of latamoxef and cefoperazone, reported to act like disulfiram in humans, caused a depression of mitochondrial low Km aldehyde dehydrogenase (low Km ALDH) activity in rats. In addition, a marked increase of blood acetaldehyde concentration was observed when rats were given alcohol orally at 18 hours after administration of these cephalosporins. However, mitochondrial low Km ALDH activity and blood acetaldehyde level were not altered by repeated administration of 300 mg and 1,000 mg of cefclidin (CFCL, E1040) or E1077 per kg. From these results, it was concluded that neither CFCLn or E1077 affected the alcohol metabolizing-system.
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PMID:[Effect of cefclidin and E1077, new cephalosporins, on the alcohol-metabolizing system in rats]. 151 19

1. Short-term treatment with tamoxifen (a nonsteroidal antiestrogen) decreased mouse spontaneous locomotor activity compared to controls. 2. Short-term pretreatment with tamoxifen prior to an acute sedative dose of ethanol potentiated ethanol-medicated behavioral depression in the mouse. 3. Injection of a small dose of Leu-enkephalin, which is devoid of effect on mouse motility, prior to an acute sedative dose of ethanol to tamoxifen pretreated female mice counteracted ethanol-produced suppression of motor activity. 4. Mouse liver aldehyde dehydrogenase was inhibited by the short-term administration of tamoxifen when given alone or preceding acute dosages of Leu-enkephalin. Concomitantly, there was an increase in blood plasma ethanol concentration from corresponding control. 5. The results of the behavioral performance test used suggest that tamoxifen possesses depressant property and exerts synergestic effect with Leu-enkephalin in antagonizing ethanol-produced behavioral depression in the mouse. 6. The enzymatic part of the study indicates an adverse metabolic influence by tamoxifen on hepatic metabolism of ethanol-derived acetaldehyde which could contribute to the potentiation of the sedative effect of ethanol.
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PMID:Leu-enkephalin, tamoxifen and ethanol interactions: effects on motility and hepatic ethanol metabolizing enzymes. 229 89

The effect of leucine enkephalin (LNK) on spontaneous locomotor activity was studied in mice of both sexes. The effect of a depressant dose of ethanol (ET) on LNK-mediated response on motility was also studied. In addition, the determination of specific activities of the hepatic enzymes primarily involved in the metabolism of ET and acetaldehyde was studied. Lactate dehydrogenase (LDH) isoenzymes were also assayed in both plasma and heart tissues. Intraperitoneal injection of LNK, 100 mg/kg, exerted behavioral depression in the male but not female mouse compared to controls. This effect was apparent for the initial 30 min posttreatment. Injection of two smaller doses of LNK, which were devoid of effect on mouse motility, prior to a depressant dose of ET counteracted ET-caused depression of motility only in the female mouse. This became apparent 30 min postdrug injection and lasted for 60 min thereafter. The LNK and ET treatment inhibited only male mouse liver aldehyde dehydrogenase in both cytoplasmic and mitochondrial preparations concomitant with reduction of plasma but not heart LDH1 isoenzyme from corresponding controls. The results suggest that LNK and ET affect different systems involved in behavioral depression tested and show a potential for LNK in antagonizing the ET effect studied. The data also indicate a sex-dependent effect of LNK on motility and of its interaction with ethanol on the enzymes studied.
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PMID:Effect of leucine enkephalin on ethanol produced behavioral depression in the mouse. 281 53

The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment. Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreatment with antibiotics. A similar time course change in the effect was obtained when disulfiram was administered. The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram-like effect was followed by a disappearance of the drugs. Secondly, the concentration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration. Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.
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PMID:Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol-metabolizing system in rats. 289 54

Aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were determined in erythrocytes of various ages, separated by Percoll gradient centrifugation, in 13 alcoholic patients and eight control subjects. The total erythrocyte activities of all three enzymes were not affected by alcoholism, however, the youngest cells of alcoholics had a decreased aldehyde dehydrogenase activity, while both glucose-6-phosphate dehydrogenase and pyruvate kinase activities were increased. The depression of aldehyde dehydrogenase activity not only persisted, but became more marked after 2 weeks of abstinence, while the enhanced activities of the two other enzymes returned to normal. These observations suggest that chronic alcohol ingestion suppresses aldehyde dehydrogenase in the bone marrow, while it enhances other erythrocytic enzymes.
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PMID:Changes in erythrocyte enzyme activities during erythrocyte aging in alcoholism. 304 74

The effect of pretreatment with amantadine (AMN) on chlorpromazine (CPZ) and reserpine (RES)-produced behavioral depression was studied in the male mouse. The effect of this treatment on hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH), which catalyze the metabolism of biogenic amine aldehydes, was also investigated. Administration of AMN, 100 mg/kg, initially decreased spontaneous locomotor activity from saline control. Pretreatment with identical dose of AMN 15 min before small dose of CPZ or RES, 0.2 mg/kg, further suppressed motility compared to animals receiving the individual AMN, CPZ or RES treatment. Using a second dose regimen of these compounds, given 5 hr post the initial injection, altered L-ALDH as a function of its subcellular localization. This was demonstrated by AMN-produced induction of mitochondrial, but not cytoplasmic L-ALDH. Likewise, a moderate but not statistically significant increase in endogenous mitochondrial L-ALDH was determined subsequent to the CPZ treatment. Treatment with AMN prior to CPZ reduced the enhancement of L-ALDH to control levels. The RES dose used was devoid of action on remainder of hepatic enzymes measured. The results indicate that AMN possesses central depressant property which was potentiated by CPZ and RES. The enzymatic data suggest antagonism between AMN and CPZ on induction of mitochondrial L-ALDH.
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PMID:Effect of amantadine on chlorpromazine and reserpine-induced behavioral depression in the mouse. 322 46

We investigated the effect of daily oral administration to young rats of lead (10 mg/kg) and ethanol (10%, v/v, in drinking water), either alone or in combination, for 8 weeks on the uptake of lead in tissues, brain biogenic amines, hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase and some selected lead-sensitive variables. Lead given in combination with ethanol produced more pronounced inhibition in the activities of hepatic glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as compared to lead alone treatment. Simultaneous exposure to lead and ethanol produced a greater depression of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the whole brain of rats, compared to rats treated with lead alone. The concentrations of lead in blood, liver and brain were significantly higher in rats exposed simultaneously to lead and ethanol. Though ethanol treatment alone inhibited the activities of hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase, no effect of lead treatment alone on these variables was observed. The results suggested that animals exposed to ethanol and lead are more vulnerable to the neurologic and hepatotoxic effects and the systemic toxicity of lead.
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PMID:Effect of combined exposure to lead and ethanol on some biochemical indices in the rat. 382 40

In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.
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PMID:Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo. 397 44


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