reamberin and 3-hydroxypyridine

The review is devoted to the assessment of the pharmacological effects of 3-hydroxypyridine and succinic acid derivatives (emoxipin, reamberin and mexidol) from the standpoint of their dopaminergic activity. A systematic analysis of the data has been performed, allowing us to consider emoxipin, reamberin and mexidol as «normalizers of dopaminergic neurotransmission», the dopaminergic action of which in its phenotype corresponds to the effects of partial dopamine receptor agonists. The position that the dopaminergic effect, antioxidant and antidepressant potential of drugs containing 2-ethyl-6-methyl-3-oxypyridine (emoxipine and mexidol) are associated with their inhibitory effect on monoamine oxidase-A (MAO-A) has been substantiated. A direct relationship between the stimulating effect of succinate-containing drugs (reamberin and mexidol) on MAO-B, their prooxidant activity, insulin-potentiating and antidepressant effects was analyzed. A hypothesis has been put forward on the general pathological significance of dopaminergic regulation disorders, the correction of which with the 3-hydroxypyridine and succinic acid derivatives can be considered as a promising strategy for improving the complex therapy of socially significant and common human diseases.. Обзор посвящен рассмотрению фармакологических эффектов производных 3-оксипиридина и янтарной кислоты (эмоксипина, реамберина и мексидола) с позиций их дофаминергической активности. Выполнен систематический анализ данных, позволяющих рассматривать эмоксипин, реамберин и мексидол в качестве «нормализаторов дофаминергической передачи», дофаминергическое действие которых соответствует эффектам частичных агонистов рецепторов дофамина. Обосновано положение о том, что дофаминергическое действие, антиоксидантный и антидепрессивный потенциал препаратов, содержащих 2-этил-6-метил-3-оксипиридин (эмоксипин и мексидол), связаны с их угнетающим влиянием на моноаминоксидазу-А. Проанализирована прямая связь между стимулирующим действием сукцинатсодержащих препаратов (реамберин и мексидол) на моноаминоксидазу-Б, их прооксидантной активностью, инсулинпотенцирующим и антидепрессивным эффектами. Выдвинуто положение об общепатологическом значении нарушений дофаминергической регуляции, коррекция которых с помощью производных 3-оксипиридина и янтарной кислоты может рассматриваться как перспективная стратегия совершенствования комплексной терапии социальнозначимых и наиболее распространенных заболеваний человека.

Topics: Dopamine; Humans; Pyridines; Succinates; Succinic Acid

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.

Topics: Animals; Anti-Anxiety Agents; Anxiety; Female; Male; Meglumine; Picolines; Pyridines; Rats; Risk-Taking; Succinates; Succinic Acid

Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

Topics: Alloxan; Animals; Conditioning, Classical; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response Relationship, Drug; Female; Hyperglycemia; Hyperlipidemias; Hypoxia; Male; Meglumine; Mice; Nootropic Agents; Picolines; Pyridines; Rats; Succinates; Thioctic Acid

A study of 3-hydroxypiridine and succinic acid derivates (emoxipin, reamberin and mexidol) effects on the 14 week dynamics of vertebral/neurologic symptoms was performed in 136 patients after the surgical treatment of disk herniations. Data obtained demonstrated the reduction of severity of neurodystrophic and radicular syndromes without significant changes in dorsalgia, psychological maladaptation (PM) and disability scores (DS) during 3.5 months in patients treated with emoxipin (150 mg i.v., daily) for two weeks after the microdiscectomy. The two-week administration of reamberin (400 mg i.v., daily) led to the early attenuation of neuropathic pain. The reduction of sings of radicular compression and DS measured with the Roland-Morris questionnaire were delayed for 3 months. Mexidol (300 mg i.v., once a day during two weeks) demonstrated the highest efficacy. This drug attenuated radicular and neurodystrophic syndromes, nociceptive and neuropathic pain, reduced PM and DS measured with both the Roland-Morris and the Oswestry questionnaires during 14 weeks after the surgery.

Topics: Adult; Female; Humans; Intervertebral Disc Displacement; Male; Meglumine; Middle Aged; Neuralgia; Picolines; Postoperative Period; Pyridines; Spine; Succinates