[Anxiolytic and antidepressant effects of emoxipine, reamberin and mexidol in experimental diabetes mellitus]. / Anksioliticheskoe i antidepressivnoe deistvie émoksipina, reamberina i meksidola pri éksperimental'nom sakharnom diabete.

AIM: To perform a comparative study of anxiolytic and antidepressant effects of derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) in experimental diabetes mellitus. MATERIAL AND METHODS: An effect of emoxipine, reamberin and mexidol on manifestations of anxiety in 'elevated plus maze' (EPM) and duration of 'desperate behavior' (DB) in Porsolt test in rats with alloxan diabetes during medication course was studied. Alpha-lipoic (thioctic) acid (α-LA) was used as a reference drug. In additional experimental series, an effect of emoxipine, reamberin, mexidol and α-LA on the intensity of hyperglycemia in experimental DM was investigated. RESULTS AND CONCLUSION: All studied medications used in doses equivalent to therapeutic range in humans and administered for 14 days significantly reduced manifestations of anxiety and depression in rats with alloxan diabetes. The most pronounced anxiolytic potential was demonstrated for emoxipine that emerged as the only medication in the study that reduced manifestations of anxiety not only in comparison with 'alloxan diabetes-control' groups but also in comparison to 'intact control'. The intensity of tranquilizing activity of derivatives of 3-oxypyridine and succinic acid was similar to that of α-LA while the thymoanaleptic activity, when the drugs were administered in maximal doses to rats with experimental DM, was higher. Both emoxipine and mexidol as well as α-LA in all studied doses significantly decreased hyperglycemia in alloxan diabetes. Reamberin demonstrated only insignificant tendencies of the same trend.

[ANTIANHEDONIC EFFECT OF 3-OXYPYRIDINE AND SUCCINIC ACID DERIVATIVES].

We performed a comparative study of the effect of original domestic derivatives of 3-oxypyri-dine and succinic acid (emoxipine, reamberin and mexidol) on measures from «sucrose preferen-ce¼ test which is used for assessment of hedonic behavior in rats. а-lipoic acid (а-LA) and amit-riptylin were used as reference medications. For the modeling of anhedonia rats received dexa-methasone (5 mg/kg subcutaneously). We established that threefold administration of emoxipine, reamberin and mexidol in doses that are equivalent to therapeutic range in humans had antianhe-donic effect and increased the measures of «preference¼ and absolute sucrose consumption. This effect was demonstrated in animals that did not receive dexamethasone as well as in rats with dexamethasone-induced anhedonia. Maximal intensity of antianhedonic effect of 3-oxypyridine and succinic acid derivatives was noted after the previous administration of dexamethasone. In rats that did not receive dexamethasone, succinate-containing medications (reamberin and mexidol) exceeded the isolated 3-oxypyridine derivative (emoxipine) in their antianhedonic potential. In case of previous dexamethasone administration 3-oxypyridine and succinic acid derivatives demonstrated equivalent antianhedonic effect that exceeded the effect of reference medications (а-LA and amitriptylin).

[Antidepressant effect of 3-oxypyridine and succinic acid derivatives (experimental study)].

OBJECTIVE: To evaluate antidepressant activity of domestic derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) in rats. MATERIAL AND METHODS: The influence of emoxipine, reamberin and mexidol on duration of desperate behavior of rats in Porsolt forced swim test was studied. Additionally the effect of these substances on the animal's behavior in the open field was evaluated. Amitriptyline and alpha-lipoic acid were used as reference substances. RESULTS: It was established that three administrations of any of the substances in doses corresponding to the therapeutic range in humans reduced the duration of desperate behavior in Porsolt test. Such effect of emoxipine, reamberin, mexidol and alpha-lipoic acid is indicative of their antidepressant activity. Intensity of this activity depends on the effect of these substances on the behavior in the open field. CONCLUSION: Reamberin and alpha-lipoic acid that in maximal doses either had no effect on the orientation behavior in the open field (reamberin) or suppressed it (alpha-lipoic acid) matched amitriptyline in the extent of antidepressant activity. The derivatives of 3-oxypyridine (emoxipine and mexidol) with stimulatory effect on the behavior in the open field demonstrated significantly lower ability to reduce desperate behavior than that of amitriptyline.

[Anxiolytic and antidepressant effects of 3-oxypiridine and succinic acid derivatives in alloxan diabetes].

The effects of 3-oxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) on affective disorders in rats with alloxan diabetes were studied. The efficiency of emoxipine, reamberin and mexidol was compared to alpha-lipoic acid, which is considered a "golden standard" in treatment of diabetic neuropathies. Emoxipine, reamberin and mexidol after seven administrations in single doses, that are equivalent to therapeutic range in humans, corrected the anxiety-depressive disorders in rats with alloxan diabetes. Unlike reamberin and alpha-lipoic acid, emoxipine and mexidol corrected the affective status concurrently with the decrease in hyperglycemia. At the same time, emoxipine outperformed mexidol in tranquilizing action (in maximal doses) but yielded mexidol in the antidepressant effect (in minimal doses).

Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives.

Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders.