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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.

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.

Objective: The effect of original domestic derivatives of 3-oxypiridine and succinic acid (emoxipine, reamberin and mexidol) on the resistance to acute brain ischemia was studied in an experimental mouse models., Material and Methods: We used 260 adult outbred mice. The drugs were introduced intraperitoneally 30 min before the modeling of acute brain ischemia. Each drug was used in 3 three doses: 1/2 of the calculated equivalent of mean treatment dose (EMTD), EMTD and double EMTD. A strangulation model with the assessment of mouse mortality latency and decapitation model with the assessment of agonal respiration (gasping) were used. The efficacy of the drugs was determined by comparison against alpha-lipoic acid that was used as a reference substance in previous studies of antihypoxic activity of emoxipine, reamberin and mexidol., Results and Conclusion: It was established that the derivatives of 3-oxipiridine and succinic acid protected against subtotal ischemia of rostral brain segments (of cerebral hemispheres) as evidenced by the increase in longevity. Emoxipine demonstrated the maximal effect thereby surpassing reamberin and mexidol in the intensity of antiischemic activity. Antiischemic effect of alpha-lipoic acid was comparable to emoxipine. In the model of total brain ischemia, the derivatives of 3-oxipiridine and succinic acid caused the opposite (proischemic) action on the bulbar respiratory center as evidenced by the reduction in duration of gasping. Alpha-lipoic acid did not affect the duration of gasping.

The effect of derivatives of 3-oxypyridine and succinic acid (emoxypine, reamberin, and mexidol) on the manifestations of anxiety (according to the criteria of behavior in elevated cross plus maze test) depression (according to the criterian of immobility in the Porsolt test) in the acute phase of alloxan diabetes (96 h after alloxan administration) has been studied in rats. The effectiveness of emoxypine, reamberin, and mexidol was compared with that of alpha-lipoic acid (etalon treatment of diabetic neuropathy). It was established that a single administration of 3-oxypyridine and succinic acid derivatives in doses equivalent to the therapeutic range for humans corrected anxio-depressive disorders in the acute phase of alloxan diabetes, while being not inferior to alpha-lipoic acid with respect to the intensity of anxiolytic and antidepressant action. The correction of affective disorders by emoxypine, reamberin and mexidol did not depend on their effect on hyperglycemia in the acute phase of alloxan diabetes. The most pronounced anxiolytic action was observed upon the administration of emoxypine, while the most pronounced antidepressant effect was observed upon the administration of mexidol.

Protective action of 3-oxypiridine and succinic acid derivatives (emoxipin, reamberin and mexidol) was studied in mice under acute alloxan-induced intoxication conditions. All these drugs exhibited protective action with respect to hyperglycemia and hyperglycemia-connected elongation of desperate behavior in the tail-suspension test and reduced activity level on the open field test. Mexidol exceeded emoxipin in the dose range of protecting action with respect to alloxan-induced hyperglycemia and was superior to reamberin in the treatment of desperate behavior in the tail-suspension test.