zimeldine and Anxiety-Disorders

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

Changes in diagnostic criteria have shown a trend towards a broader definition of depression. Thus, a number of patients who would previously have been considered to be suffering from anxiety states are now classified as having major depressive illness according to the criteria of the Diagnostic Statistical Manual III. Despite this, such patients show a good response to antidepressant drugs (compared to placebo) if their severity of depression is above 15 on the Hamilton depression scale. It therefore seems likely that there is a common biological substrate underlying both anxiety states and depressive illness, but this issue remains somewhat controversial. The suggestion that the 5-HT system is involved in the mediation of anxiety is considered. Further evidence is required before definite conclusions can be drawn, but it seems clear that anxiolytic activity is not dependent on sedative properties.

Topics: Amitriptyline; Anxiety Disorders; Depressive Disorder; Humans; Serotonin; Sleep Initiation and Maintenance Disorders; Zimeldine