sm-346 and Anxiety-Disorders

Afobazole was administered to 32 patients, aged 18-60 years, with cardio-vascular diseases and neurotic stress-related psychopathologies and somatoform disorders (ICD-10 F40-F45). The drug was assigned in dosages from 30 to 60 mg daily (mean 50 mg) during 6 weeks, along with basic somatotropic therapy. Twenty-nine patients completed the course. Therapeutic efficacy was assessed by the Hamilton anxiety scale (HAM-A) and a subscale of the Global Clinical Impression scale (CGI). The total number of responders was 21 (70%). The improvement began from the 1st week of the treatment and increased to the 42nd day. At the same time, intensity of mental disorders (phobic, somatisized, anxiety-depressive) gradually decreased up to complete reduction. Afobazole was well-tolerated by patients.

Topics: Adolescent; Adult; Anxiety Disorders; Benzimidazoles; Cardiovascular Diseases; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Treatment Outcome

A standardized clinical and pharmacological trial of the peculiarities of action and efficacy of aphobazol, a new anxyolytic with non-benzodiazepine structure, has been conducted. An effect of the drug on different anxiety disorders has been studied. It is shown that combined anxyolytic and activating action exerted the main effect. The best efficacy of aphobazol was found in anxiety disorders of "simple" structure. In more complicated anxiety disorders, aphobazol efficacy depended on the correlation between clinical appearances of deeper registers and anxiety affect. The best results have been achieved in patients with acute anxiety-phobic disorders, in the structure of which sensible anxiety with episodes of generalization, dominating vivid ideas, sensibly saturated phobias with pronounced autonomic disorders and senestalgias prevailed. In case of chronic disease course, with formation of more inert, "complex" in structure and deep by register psychopathological disorders (cognitive character of anxiety, appearances of agoraphobia and avoidance behavior, heteronomous body sensations and hypochondriac activity), the efficacy of aphobazol treatment was significantly lower. In this case a therapy combined with selective inhibitors of serotonin reuptake and neuroleptics is needed.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Benzimidazoles; Female; Health Status; Humans; Male; Middle Aged; Morpholines; Psychological Tests; Severity of Illness Index

Long-term administration of benzodiazepines is known to be associated with drug dependence. The aim of the present work was to investigate the effects of non-benzodiazepine anxiolytic afobazole in the treatment of benzodiazepine withdrawal syndrome. Male outbred rats were treated with either diazepam (4.0 mg/kg, i.p.) or vehicle for 30 days and then abruptly withdrawn for 48 h. Animals were tested in the elevated plus maze test. In addition, neurochemical shifts were evaluated in the selected brain structures (striatum, hippocampus, hypothalamus, and frontal cortex) during diazepam withdrawal. Withdrawn animals made fewer entries and spent less time on the open arms than did vehicle-treated rats and demonstrated a decrease in the dopamine level in striatum as compared with vehicle and diazepam-treated ones. Afobazole (5.0 mg/kg, i.p.) effectively (i) ameliorated withdrawal-induced anxiety, returning behavioral pattern in the elevated plus maze test up to levels comparable to that in vehicle-treated animals, and (ii) increased withdrawal-reduced dopamine level (+23.8%, p < 0.05) in striatum. It is suggested that afobazole, due to its multitarget receptor action, can be useful in the diazepam withdrawal-induced anxiety blockade through modulation of dopaminergic system activity.

Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Behavior, Animal; Benzimidazoles; Brain; Brain Chemistry; Diazepam; Male; Maze Learning; Morpholines; Rats; Substance Withdrawal Syndrome

Pharmacokinetics of compound M-11 (main metabolite of afobazole) after administration via different routes was studied in rats. After oral and intravenous administration, M-11 exhibited weakly pronounced bioconversion with the formation of a few metabolites that could be detected in plasma samples for about 3 hours. The absolute bioavailability of M-11 after oral administration was 68.3%. It was found that M-11 was completely absorbed from gastrointestinal tract of rats and characterized by "the first pass effect", after which approximately 70% of administered dose entered the circulation. The parent substance was determined neither in urine nor in feces.

Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Area Under Curve; Benzimidazoles; Biological Availability; Biotransformation; Chromatography, Liquid; Feces; Gastrointestinal Tract; Half-Life; Infusions, Parenteral; Injections, Intravenous; Limit of Detection; Male; Morpholines; Rats; Tandem Mass Spectrometry

Topics: Aged; Anti-Anxiety Agents; Anxiety Disorders; Benzimidazoles; Brain Ischemia; Female; Humans; Male; Middle Aged; Morpholines; Treatment Outcome

To study afobasol efficacy in anxiety and neurotization correction in patients with celiac disease (CD).. We examined 17 CD patients with mental diseases (anxiety, anxiophobic and neurotic disorders) aged 35.3 +/- 3.5 years. Personal and situational anxiety levels were assessed with multivariate questionnaire of the integrative anxiety test, neurotization--with Wasserman's questionnaire. Mental diseases were treated for 4 weeks with afobasol in a daily dose 30 mg.. An initial level of personal anxiety was elevated in 100% patients, of situational anxiety--in 66.7%. These kinds of anxiety (most of all general, emotional discomfort, asthenic and phobic components) were treated with a positive effect. Neurotization was high in 11 patients. The treatment was effective in 6 of them. Side effects were not noted. The highest reduction was seen in emotional discomfort, asthenic component and anxiety.. Afobasol is effective in management of mental diseases in patients with celiac disease.

Topics: Adult; Anxiety Disorders; Benzimidazoles; Celiac Disease; Drug Administration Schedule; Female; Humans; Male; Mental Disorders; Morpholines; Phobic Disorders; Psychological Tests; Severity of Illness Index