zimeldine and Alcoholism

zimeldine has been researched along with Alcoholism* in 9 studies

Reviews

5 review(s) available for zimeldine and Alcoholism

ArticleYear
Serotonin uptake inhibitors attenuate ethanol intake in problem drinkers.
    Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism, 1989, Volume: 7

    There are several problems with the drugs currently used to decrease alcohol consumption (i.e., alcohol-sensitizing drugs, such as disulfiram). Their efficacy is unproven, they are associated with toxicity, and there are several contraindications for use. New therapies are needed because alcohol-related problems affect almost 20% of the adult population. A new strategy was developed that involves attenuation of alcohol intake via serotonin uptake inhibitors. Since several experiments showed that serotonin uptake inhibitors consistently attenuated ethanol intake in rats, we tested their effects in humans. In four randomized, double-blind, placebo-controlled studies serotonin uptake inhibitors (zimelidine, citalopram, viqualine, and fluoxetine) decreased total number of drinks consumed by early stage problem drinkers by an average of 20-30%. However, marked interindividual variations in the pattern of response to serotonin uptake inhibitors have been observed, and we have been unable to identify subject traits or drug factors that predict pattern of response. Effects on ethanol intake are distinct from the antidepressant properties of these drugs, and they are most likely due to facilitation of satiety signals. Because of these promising and consistent results, further testing in a therapeutic context is under way. Serotonin uptake inhibitors suggest an innovative approach for moderating ethanol intake in problem drinkers.

    Topics: Alcohol Drinking; Alcoholism; Brain; Citalopram; Clinical Trials as Topic; Humans; Receptors, Serotonin; Serotonin Antagonists; Zimeldine

1989
Serotonin and alcohol: interrelationships.
    Psychopathology, 1989, Volume: 22 Suppl 1

    Alcoholism is a multifaceted medicosocial problem. Recent literature discusses a common dyad, alcoholism and anxiety. Both disorders are interdigitated with the brain amine serotonin (5-hydroxytryptamine, 5-HT). Direct 5-HT activation reportedly attenuates alcohol consumption, whereas depletion enhances use patterns. Acute alcohol consumption has also been associated with a transient rise, albeit eventual diminished 5-HT turnover. A variety of 5-HT models have confirmed this observation, e.g., reduced platelet 5-HT content, uptake, and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid. Such altered characteristics of 5-HT secondary to chronic alcohol use may explain the frequent morbidity of anxiety and/or depression. Acute alcohol consumption is also associated with accumulation of the 5-HT aldehyde derivative 5-hydroxymethtryptoline. Thus, alcohol may induce the in vivo formation of aldehydes, e.g., beta-carbolines, that themselves possess high lipophilicity and psychotropic activity. Future investigation into 5-HT-specific pharmacologic probes in alcoholism will be interesting. Preliminary research has consistently demonstrated that 5-HT-enhancing agents (e.g., zimelidine or fluvoxamine) decrease alcohol consumption, preference, and short-term memory decrements. Thus, 5-HT appears to represent at least one common denominator for a spectrum of behavioral disorders including anxiety and alcoholism.

    Topics: Alcohol Drinking; Alcoholism; Animals; Anti-Anxiety Agents; Anxiety Disorders; Arousal; Brain; Fluvoxamine; Humans; Oximes; Receptors, Serotonin; Serotonin; Zimeldine

1989
Pharmacological treatment of alcohol intoxication, withdrawal and dependence: a critical review.
    Journal of studies on alcohol, 1987, Volume: 48, Issue:4

    This review critically examines the literature of the past 10 years relating to the use of drugs in treating alcohol intoxication, withdrawal and dependence. Emphasis is given to those studies that have current and potential future clinical relevance. Although research regarding the pharmacological treatment of alcohol disorders still suffers from methodological flaws and lukewarm acceptance, the recognition of this area as a legitimate and fruitful field of study is increasingly apparent.

    Topics: Alcohol Deterrents; Alcoholic Intoxication; Alcoholism; Antidepressive Agents, Tricyclic; Bromocriptine; Cyanamide; Disulfiram; Ethanol; Fenfluramine; Humans; Lithium; Nitroimidazoles; Substance Withdrawal Syndrome; Sympathomimetics; Taurine; Tranquilizing Agents; Zimeldine

1987
Modulation of ethanol intake by serotonin uptake inhibitors.
    The Journal of clinical psychiatry, 1986, Volume: 47 Suppl

    The most commonly prescribed agents for decreasing ethanol intake are alcohol-sensitizing drugs; however, their efficacy is unproven, they are associated with toxicity, and there are several contraindications for use. A program to identify and test new drugs to decrease ethanol intake has focused on drugs that enhance central serotonergic neurotransmission and consistently attenuate ethanol consumption. Animal studies have shown consistent findings with direct and indirect serotonin (5-HT) agonists. Ethanol intake decreased after the administration of 5-HT precursors, 5-HT uptake inhibitors, intracerebral 5-HT, and postsynaptic 5-HT agonists; in contrast, destruction of serotonin-containing neurons with 5,6- or 5,7-dihydroxytryptamine increased ethanol intake. Administration of zimelidine (200 mg/day p.o.) to 16 healthy alcohol abusers was associated with a significant increase in number of abstinent days and a decrease in number of drinks consumed. Approximately 50% of the subjects were responders, 35% were partial responders, and 10%-15% were nonresponders. In a recent double-blind crossover study, citalopram, an even more selective serotonin uptake inhibitor, produced similar results. Because serotonin uptake inhibitors acted rapidly and subjects were not clinically depressed, this action is distinct from antidepressant effects. These drugs most likely interfere with the neurobiologic mechanisms regulating ethanol intake and provide an innovative approach for modulating the use of alcohol in problem drinkers.

    Topics: Acetaldehyde; Alcohol Drinking; Alcoholism; Animals; Brain; Citalopram; Disulfiram; Dopamine; Humans; Propylamines; Rats; Receptors, Serotonin; Serotonin; Synaptic Transmission; Zimeldine

1986
Zimeldine: a review of its effects on ethanol consumption.
    Neuroscience and biobehavioral reviews, 1984,Spring, Volume: 8, Issue:1

    This review evaluates the literature and describes an extensive series of experiments which examined the effects of zimeldine , its metabolite norzimeldine and other serotonin and norepinephrine reuptake inhibitors on voluntary ethanol consumption in rats. The results of these experiments indicate that drugs which specifically inhibit serotonin reuptake are capable of decreasing voluntary ethanol consumption. The behavioral mechanism through which these drugs exert their effects seems to be extinction of the primary reinforcing properties of alcohol. These effects seem to be partially attenuated both by drugs which modulate the norepinephrine system as well as by the serotonin postsynaptic receptor blocker methergoline. The data presented in this review are discussed in terms of the involvement of the serotonin and norepinephrine systems in the mechanism of action of these drugs. In addition, several alternative hypotheses concerning the nature of the phenomenon are offered. Finally, the implications of these data for the possible development of a treatment procedure for problem drinkers is discussed.

    Topics: Alcohol Drinking; Alcohol Withdrawal Delirium; Alcoholism; Animals; Appetitive Behavior; Extinction, Psychological; Humans; Morphine Dependence; Motivation; Norepinephrine; Rats; Receptors, Adrenergic; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Zimeldine

1984

Trials

2 trial(s) available for zimeldine and Alcoholism

ArticleYear
Serotonin uptake inhibitors attenuate ethanol intake in problem drinkers.
    Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism, 1989, Volume: 7

    There are several problems with the drugs currently used to decrease alcohol consumption (i.e., alcohol-sensitizing drugs, such as disulfiram). Their efficacy is unproven, they are associated with toxicity, and there are several contraindications for use. New therapies are needed because alcohol-related problems affect almost 20% of the adult population. A new strategy was developed that involves attenuation of alcohol intake via serotonin uptake inhibitors. Since several experiments showed that serotonin uptake inhibitors consistently attenuated ethanol intake in rats, we tested their effects in humans. In four randomized, double-blind, placebo-controlled studies serotonin uptake inhibitors (zimelidine, citalopram, viqualine, and fluoxetine) decreased total number of drinks consumed by early stage problem drinkers by an average of 20-30%. However, marked interindividual variations in the pattern of response to serotonin uptake inhibitors have been observed, and we have been unable to identify subject traits or drug factors that predict pattern of response. Effects on ethanol intake are distinct from the antidepressant properties of these drugs, and they are most likely due to facilitation of satiety signals. Because of these promising and consistent results, further testing in a therapeutic context is under way. Serotonin uptake inhibitors suggest an innovative approach for moderating ethanol intake in problem drinkers.

    Topics: Alcohol Drinking; Alcoholism; Brain; Citalopram; Clinical Trials as Topic; Humans; Receptors, Serotonin; Serotonin Antagonists; Zimeldine

1989
Limitations in the measurement of urine ethanol in clinical trials to monitor ethanol consumption.
    Journal of studies on alcohol, 1988, Volume: 49, Issue:6

    Self-report of daily alcohol consumption has been used as the dependent variable in clinical trials to assess the effects of two serotonin uptake inhibitory drugs, zimelidine and citalopram. The validity of the dairy data was established by correlating concentration of ethanol in daily urine samples with number of reported standard alcoholic drinks (r = 0.62 for the 934 subject-days in the zimelidine study; r = 0.54 for the 3,103 subject-days in the citalopram study, both p less than 0.0001). The effects of factors other than inaccurate reporting, such as the range of values for reported daily drinks and subjects' drinking patterns, on the correlation coefficients for all subject-days and for individual subjects in the citalopram study are discussed. Sampling 50% or fewer of the 84 days of the citalopram study for each subject is economically advantageous and did not significantly change the values of the correlation coefficients or the rank positions of subjects but did increase the 95% confidence intervals for the correlation coefficients, indicating less certainty about the actual correlation coefficients and, therefore, the accuracy of a subject's self-report. The ability of urine ethanol concentration to validate objectively diaries of alcohol consumption is limited by factors that must be considered but are likely to be out of the investigator's control.

    Topics: Adult; Alcohol Drinking; Alcoholism; Citalopram; Clinical Trials as Topic; Double-Blind Method; Ethanol; Humans; Male; Truth Disclosure; Zimeldine

1988

Other Studies

3 other study(ies) available for zimeldine and Alcoholism

ArticleYear
Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake.
    Drug and alcohol dependence, 1994, Volume: 35, Issue:3

    In an open study, 14 alcohol-dependent male patients were treated with the selective serotonin reuptake inhibitor (SSRI) Zimelidine, 200 mg daily, for six months. They were given psychosocial therapy before and during the study. The number of days of alcohol intake was statistically significantly reduced from a mean of 14 days per month before to 1-5 days during drug treatment. No effect was observed on the amount of daily alcohol intake on drinking days. No tolerance to the effect of Zimelidine was observed during the study. The findings suggest an effect of combined psychosocial support with SSRI treatment that seems to be of clinical significance.

    Topics: Adult; Alcohol Drinking; Alcohol Withdrawal Delirium; Alcoholism; Combined Modality Therapy; Humans; Liver Function Tests; Male; Middle Aged; Psychotherapy; Zimeldine

1994
Pharmacokinetics of zimeldine in male alcoholics.
    Acta pharmacologica et toxicologica, 1986, Volume: 59, Issue:2

    The pharmacokinetics of zimeldine, a 5-HT reuptake blocker with antidepressive effects, was studied after a single oral dose and after multiple oral administration in 19 alcoholic males, 10 with and 9 without chronic liver damage. The average plasma concentration of zimeldine as assessed by the AUC values (area under the plasma concentration-time curve) was significantly higher in the chronically liver damaged patients than in the patients without chronic liver damage. The plasma half-life of zimeldine was also significantly longer in the chronically liver damaged patients. There were no differences in the obtained pharmacokinetic parameters between the patients having nonchronic liver damage and healthy control subjects. The pharmacokinetics of the active metabolite norzimeldine (resulting from N-demethylation of zimeldine) showed no differences between the two groups of alcoholics and the healthy controls. The IgA values were significantly correlated to both the AUC and plasma half-life of zimeldine. No other correlation between clinical chemistry parameters and pharmacokinetic parameters of zimeldine and norzimeldine were found.

    Topics: Adult; Alcoholism; Blood Proteins; Cholesterol; Enzymes; Half-Life; Humans; Kinetics; Liver Diseases, Alcoholic; Male; Middle Aged; Triglycerides; Zimeldine

1986
Therapeutic use of serotonergic drugs in alcohol abuse.
    Clinical neuropharmacology, 1986, Volume: 9 Suppl 4

    Topics: Alcohol Drinking; Alcoholism; Animals; Biomechanical Phenomena; Citalopram; Propylamines; Rats; Serotonin; Zimeldine

1986