Effect Of Semax Research Articles

Paradoxical influence of combined effect of Semax and ammonium molybdate on learning and memory in rats

The combined effect of Semax with water solutions of plumbum diacetate (10–7 M) and ammonium molybdate (10–5 M) on the two-way active avoidance learning in rats in the shuttle chamber was studied. It was established that both salts of heavy metals oppress the learning and memory; plumbum diacetate caused larger oppression. Semax slowed down the development of the conditioned response but counteracted the negative influence on this process from the side of both metals. The effect of Semax on the development of the avoidance reaction in the presence of ammonium molybdate, which oppressed the avoidance by itself, paradoxically intensified. During the combined effect of the peptide and ammonium molybdate, the development of the conditioned reaction occurred much faster than against the background of Semax without the combination with molybdenum. In total, data obtained indicate a counteraction of Semax to neurotoxic effect of plumbum and molybdenum salts. Since oxidative stress is the main mechanism of neurotoxic effect of heavy metals, the indicated positive effect of Semax can, in our opinion, confirm the presence of antioxidant properties in the spectrum of the peptide pharmacological activity.

Cplx2 gene expression following semax or PGP administration under conditions of two experimental models of rat-brain ischemia

Complexin 2 is a cytosolic protein participating in synaptic-vesicle exocytosis. The RT-PCR technique was used in a real-time study of the dynamics of variation of expression of the Cplx2 gene that encodes this protein. The study was performed in the rat brain. Measurements under the conditions of incomplete global ischemia were performed during 1 day; measurements under the conditions of focal ischemia were carried out 3, 24, and 72 h after irreversible occlusion of the medial cerebral artery. The most significant decrease in Cplx2 transcripts under the conditions of incomplete global ischemia was observed in the hippocampus and the frontal cortex of rats 12 and 24 h after irreversible occlusion of the common carotid arteries, respectively. Under conditions of focal ischemia, a decrease in the content of Cplx2 transcripts was observed only in focal lesions of the frontoparietal cortex 24 h after occlusion. The effect of Semax neuroprotector peptide and its C-terminal fragment Pro-Gly-Pro on Cplx2 expression was examined under the model ischemia conditions. In the case of incomplete global ischemia, application of Semax compensated for the maximum decrease in Cplx2 expression in the frontal cortex and hippocampus in rats caused by lesions. However, the peptide had no effect when used in rats with focal ischemia. The effect of PGP on Cplx2 expression under conditions of experimental ischemia was more complicated and did not always coincide with the effect of Semax. The obtained results provide insight into the specific features of Cplx2 expression under the conditions of experimental brain ischemia and help to better understand the mechanisms of activity of peptide preparations.

Semax prevents learning and memory inhibition by heavy metals.

Separate and joint effect of Semax, ascorbic acid, lead diacetate, and ammonium molybdate on avoidance conditioning in rats was studied. It was established that the heavy metal salts inhibited the avoidance response, and the peptide counteracted this inhibition as strongly as ascorbic acid or to a comparable degree. These findings confirm the antioxidant properties of Semax.

Modulating Effect of Peptide Semax on the Level of Synaptic Activity and Short-Term Plasticity in Glutamatergic Synapses of Co-Cultured Dorsal Root Ganglion and Dorsal Horn Neurons of Rats

The effects of a long-term culturing (12 days, in vitro) of the dorsal root ganglion (DRG) and the dorsal horn (DH) neurons with peptide Semax on the level of synaptic activity in co-cultures, as well as short-term plasticity in sensory synapses were studied. It has been revealed that neuronal culturing with peptide at concentrations of 10 and 100 µM leads to increasing the frequency of spontaneous glutamatergic postsynaptic currents in DH neurons by 71.7 ± 1.8% and 93.9 ± 3.1% (n = 6; P < 0.001). Semax does not exert a pronounced effect on the amplitude and frequency of miniature glutamatergic currents, but it causes an increase of the amplitudes of spontaneous postsynaptic currents and an elevation of the quantum content. The data obtained indicate the increase in multivesicular glutamate release efficiency in neural networks of co-cultures following incubation with the peptide. Moreover, Semax (10 and 100 µM) induces changes in the basic parameters of short-term plasticity of sensory synapses, namely, i) an increase in the paired-pulse ratio from (0.53 ± 0.028) (n = 8) to (0.91 ± 0.072) (n = 6, P < 0.01) and (0.95 ± 0.026) (n = 7; P < 0.001); ii) reduced coefficients of variation ratio (CV2/CV1) from (1.49 ± 0.11) (n = 8) to (1.02 ± 0.09) (n = 6; P < 0.05) and (1.11 ± 0.13) (n = 7; P < 0.01) respectively. The results indicate a stimulating effect of Semax on the activity of glutamatergic synapses in neural networks of co-cultures, as well as the ability of the peptide to modulate effectively short-term plasticity of sensory synapses.

Semax-Induced Changes in Growth Factor mRNA Levels in the Rat Brain on the Third Day After Ischemia

The peptide Semax effectively protects brain tissues against ischemic stroke. However, the molecular mechanisms that underlie its action remain unknown. We used the focal cerebral ischemia rat model with permanent middle cerebral artery occlusion (pMCAO). During the experiments, animals were given intraperitoneal injections of Semax, Pro-Gly-Pro, or saline. We studied the effect of the peptides on the expression of more than 80 growth factor genes in the cortex. As a response to Semax administration, alterations in the expression of growth factor genes were detected at 3, 24, and 72 h after pMCAO. The most pronounced effects of Semax, i.e., the downregulation of the transcripts of 20 genes and the upregulation of 12 growth factor genes, were observed 3 days after artery occlusion. According to our data, Semax promoted the upregulation (by ≥10-fold) of the Csf3 and Artn genes, as well as of the cytokine genes Il1b and Il6. The peptide products of these genes have regulatory properties and exert neuroprotective effects in injured brain tissues. We presume that Semax triggers neuroprotective mechanisms by affecting these systems via the regulation of the expression of growth factor genes.

EFFECT OF PEPTIDE SEMAX ON SYNAPTIC ACTIVITY AND SHORT-TERM PLASTICITY OF GLUTAMATERGIC SYNAPSES OF CO-CULTURED DORSAL ROOT GANGLION AND DORSAL HORN NEURONS

The influence of long-term culturing (12 days in vitro) of dorsal root ganglion (DRG) and dorsal horn (DH) neurons with peptide Semax on the level of synaptic activity at co-cultures, as well as short-term plasticity in sensory synapses were studied. It has been shown that neuronal culturing with peptide at concentrations of 10 and 100 µM led to increasing the frequency of spontaneous glutamatergic postsynaptic currents in DH neurons to 71.7 ± 1.8% and 93.9 ± 3.1% (n = 6; P < 0.001); Semax has a not significant effect on the amplitude and frequency of miniature glutamatergic currents, but causes an increase of the amplitudes of spontaneous postsynaptic currents, as well as elevates the quantum content. The data show the increase of multivesicular glutamate release efficiency in neural networks of co-cultures following incubation with the peptide. Also Semax (10 and 100 µM) induces changes of the basic parameters of short-term plasticity in sensory synapses: (1) increasing the paired-pulse ratio from 0.53 ± 0.028 (n = 8) to 0.91 ± 0.072 (n = 6, P < 0.01) and 0.95 ± 0.026 (n = 7; P < 0.001); (2) reducing the ratio of the coefficients of variation (CV2/ CV1) from 1.49 ± 0.11 (n = 8) to 1.02 ± 0.09 (n = 6; P < 0.05) and 1.11 ± 0.13 (n = 7; P < 0.0) respectively. The results indicate a stimulating effect of Semax on the activity of glutamatergic synapses in neural networks of co-cultures, as well as the ability of the peptide to effectively modulate the short-term plasticity in sensory synapses.

Differently Directed Influences of Semax on the Formation and Functional Impairments of an Active Avoidance Reaction in Rats

The effects of Semax on the formation of a conditioned active avoidance reaction were studied in rats using different experimental models. I.p. administration of Semax at a dose of 0.05 mg/kg was found to accelerate the acquisition of a one-way conditioned avoidance reaction in a model of an active pain stimulus avoidance reflex in which the animals had to jump onto a shelf. In animals trained in a shuttle box, the peptide increased the threshold current required to provoked movement of the rats across the chamber and slowed acquisition of a two-way active avoidance reaction. Semax stimulated reproduction of the avoidance reaction in the shuttle box in rats after functional impairment induced by acute changes in cause-effect and spatial relationships in the experimental environment. These data support the view that this peptide has nootropic properties.

Pharmacological correction of amnesticdisorders in mammalians(evolutionary aspects of investigation)

The present work is devoted to the study of the peptides bioregulators of new generation (Cortexin, Semax, Selank) in the compensation of the disturbed Higher Nervous Functions ih the ascending row of mammls (insectivores, rodents, primates). The new data have been established that at the early stage of mammals (in insectivores) Cortexin, Semax and Selank induced the more significant and long lasted effect on inherent forms of behaviour. Their effects on the compensation of the disturbed Higher Nervous Functions have nonspecific, facilatory short time lasted character. Contrary to insectivores, rodents have a clear tendency to compesation for Higher Nervous Function disturbances. At the Semax and Selank background, the delayed conditional reflexes were restored. It has been established that the cerebroprotective effects of Selank exerted more significant influences upon the brain function disturbances in neurotic rats. Contrary to the results found in lower mammals, the application of Cortexin, Semax and Selank to neurotic monkeys exerted differnt effects upon the Higher Nervous Functions disturbances. The compensatory effects of drugs are dose dependant in nature being more effective with intranasal administration and having different effects on the various types of neurosis. The long duration compensation of the mental disturbances (the EEG homeostatic parameters of memory processes) took place during the Selank (30 mkg/ kg) administration. The cerebroprotective effects of Semax are especially significant on the operative memory. Cortexin antiamnestic and cerebroprotective effects especially significant at the inhibitory type of neurosis. The data collected on the compensatory Cortexin, Semax and Selank influeces on the disturbed memory processes and cognitive deficit of monkey’s may serve as neurophysiological basis for the more intensive and specific role of these drugs in the neurological clibic.

Effect of peptide Semax and its C-terminal fragment PGP on Vegfa gene expression during incomplete global cerebral ischemia in rats

Vascular endothelial growth factor (VEGF-A) is hypoxia-inducible signal glycoprotein. VEGF-A induces vascular endothelial cell proliferation, which leads to the reconstitution of the vascular network in brain regions damaged by ischemia. However, this protein is also involved in the processes of inflammation and edema in early stages of ischemia. The synthetic peptide Semax has neuroprotective and anti-inflammatory properties and is actively used in the treatment of cerebral ischemia. We have previously shown that Semax reduces vascular injury and activates the mRNA synthesis of neurotrophins and their receptors during global cerebral ischemia in rats. In this work, we studied the effect of Semax and its C-terminal Pro-Gly-Pro tripeptide on Vegfa mRNA expression in different regions of the rat brain after 0.5, 1, 2, 4, 8, 12 and 24 h, which is the irreversible occlusion of the common carotid arteries. It was shown that ischemia increases the levels of Vegfa mRNA in rat brains (4 h after occlusion in cerebellum, cerebral cortex, and hippocampus; 8 h after occlusion in the cortex and hippocampus; and 24 h after occlusion in the cortex). Treatment with Semax reduces the levels of Vegfa mRNA in the frontal cortex (4, 8 and 12 h after occlusion) and the hippocampus (2 and 4 h after occlusion). The effect of PGP on the Vegfa gene expression was almost negligible. It was shown that Semax prevents the activating effect of hypoxia on the expression of the Vegfa gene at early stages of global cerebral ischemia. In turn, an increase in the level of Vegfa mRNA in the hippocampus 24 h after occlusion and Semax administration apparently reflects the neuroprotective properties of the drug.

Влияние пептидов семакс и PGP на экспрессию генаVegfaу крыс в условиях неполной глобальной ишемии головного мозга

Vascular endothelial growth factor (VEGFA) is a hypoxia-inducible signal glycoprotein. VEGFA causes vascular endothelial cell growth and proliferation, that leads to the regeneration of vascular network in brain regions damaged by ischemia. However, this protein is involved in processes of inflammation and edema in early stages of ischemia. Synthetic peptide semax shows neuroprotective and anti-inflammatory properties and is actively used in the treatment of ischemia.We have previously shown that semax reduces vascular injury and activates the mRNA synthesis of neurotrophins and their receptors under global cerebral ischemia in rats. Here we have analyzed the effects of semax and its C-terminal Pro-Gly-Pro tripeptide upon Vegfa mRNA expression in different rat brain regions after common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. It was shown that ischemia increases levels of Vegfa mRNA in the rat brain of animals (4 h after the occlusion--in the cerebellum, cerebral cortex and hippocampus, 8 h--in the cortex and hippocampus, and 24 h in the cortex). Semax treatment reduces Vegfa mRNA levels in the frontal cortex (4, 8 and 12 h after the occlusion) and hippocampus of ischemic rats (2 and 4 h). Effect of PGP on the Vegfa gene expression was almost negligible. Our results showed that semax prevents activating effect ofhypoxia on the Vegfa gene expression in early stages of global ischemia. Furthermore, increase in the level of mRNA Vegfa in the hippocampus (24 h after occlusion) perhaps reflects neuroprotective properties of this drug.

Semax prevents functional impairments of avoidance response in rats

ACTH/MSHrelated peptides, known as melanocortins, play an important role in regulation of manyfunctions in the body, including CNS. Among melanocortins, Semax is very prominent because it is anootropic analogue of ACTH (4–10) with prolongedaction [1]. In experiments with animals, the beneficialeffects of Semax on learning with positive reinforcement have been repeatedly reported [2]. Data on theSemax effects on animal learning with negative reinforcement are very few and contradictory. Data onboth learning improvement [3] and no effect [4] havebeen published.Mixed effects of nootropic drugs on learning arewell known [5, 6]; therefore, different approachesimpairing learning and memory, such as maximalelectroshock, ischemia or frontal lobectomy [7] areused for study of nootropic properties of substances.We suppose that use of models without any excessivemethodical complications and extreme physical treatment is very promising. For this purpose, functionalimpairments of the conditioned response of activeavoidance of pain stimulation in rats were suggested[8]. They are based on modification of definite cause–effect, i.e., “avoidance response failure,” and spatialrelationships in experimental environment.Here, we studied the effects of Semax on the development of avoidance conditioning in rats and its functional impairments modeled using failure and spatialmodification approaches.MATERIALS AND METHODSTwentysix male outbred albino rats weighing 250–370 g were used for the experiment. The animals weredaily trained for active avoidance conditioning in ashuttlebox for 7 days. Each daily session consisted of25 stimulus presentations. A shuttlebox was equippedwith a partition with two doors. During training, thedistal door in the partition was opened. The followingprotocol was used for training: a rat was placed into acompartment of the shuttlebox, the conditionedstimulus (tone) was presented, and, 10 s later, theunconditioned stimulus (electroshock) was presented.Crossing to the opposite compartment in response tothe conditioned stimulus was regarded as a conditioned avoidance response. Daily, we recorded thenumber of avoidances and expressed them as percentof the total number of stimulus presentations. On thelast day of training, we used the protocol of avoidancefailure after 20 stimulus presentations. For this purpose, during 5 last stimulus presentations, we did notturn off stimuli when the rat crossed to another compartment in response to conditioned or unconditionedstimuli, and it was subjected to electroshocks. After thefifth presentation, electroshock was stopped immediately, whereas the tone was turned off 2 s later. Then,20 presentations were used for testing of avoidanceresponse under the initial conditions. Since behavioralchanges appeared immediately after functionalimpairment, we analyzed the time course of changesin the indices of avoidance conditioning in blocks of 5presentations.Failure is reversible functional impairment thatallows using the same animals to study consequentlythe effects of nootropics under the conditions of oneand the other model and to obtain a reproducible nootropic effect [9]. Based on this assumption, we reproduced avoidance response one day after its failure.Then we closed the distal door, opened the proximaldoor, and tested avoidance response recall under newconditions during 20 stimuli presentations.Thirty minutes prior to each experiment, we intraperitoneally injected a Semax solution at a dose of0.05 mg/kg in a volume of 1 mL/kg. Control animalswere injected with an equal volume of distilled water.Data in figures are presented as the means andstandard errors.

Antistress Effect of Semax in the Course of Recovery of Spleen Lymphoid Structures after the Stress in Rats with Different Behavioral Activity

We studied the effect of antistress peptide Semax, an ACTH4-10 analogue, on the cellular composition of spleen lymphoid structures in Wistar rats with different stress tolerance in the course of post-stress recovery (days 1, 3, 14, and 30). Preliminary administration of Semax alleviates stress-induced proliferation of macrophages and destructive processes in functionally active zones of the rat spleen on days 1, 3, and 14 after the stress exposure, which attests to its capacity to reduce the adverse effects of 1-h stress load on proliferation of macrophages and destructive processes in functionally active zones of this organ.

Effect of Semax and its C-terminal Fragment Pro-Gly-Pro on the Expression of VEGF Family Genes and their Receptors in Experimental Focal Ischemia of the Rat Brain

The synthetic peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is used successfully in acute stroke therapy. In spite of numerous studies on the subject, many aspects of the neuroprotective effects of the peptide remain unknown. We studied the action of Semax and its C-terminal tripeptide Pro-Gly-Pro on the expression of the VEGF gene family (Vegf-a, Vegf-b, Vegf-c, Vegf-d, and Plgf) and their receptors (Vegfr-1, Vegfr-2, and Vegfr-3) in the frontoparietal cortex region of the rat brain at 3, 24, and 72 h after permanent left middle cerebral artery occlusion (pMCAO). The relative mRNA level of the genes studied was assessed using real-time reverse transcription-PCR. The Vegf-b and Vegf-d genes were most affected by the peptides, which resulted in their most noticeable activation at 3 h after pMCAO. The level of Vegf-d transcripts decreased considerably, whereas the mRNA level of the Vegf-b gene was significantly increased after 72 h of treatment with each of the peptides. In addition, the effects of the peptides on the expression of the Vegf-b and Vegf-d genes were the opposite of the action of ischemia. It is suggested that the identified effects of the peptides diminish the effects of ischemia, thus participating in the positive therapeutic effect of Semax on ischemic stroke.

The Nootropic and Analgesic Effects of Semax Given via Different Routes

The heptapeptide Semax (MEHFPGP) is an analog of the fragment ACTH(4–10) with long-lasting actions. The aim of the present work was to study the effects of Semax on learning ability and pain sensitivity in white rats given different doses via the intraperitoneal and intranasal routes. The nootropic effects of Semax were studied in a test based on the acquisition of a conditioned passive avoidance reaction to pain stimulation. Pain sensitivity was assessed in a hindpaw compression test. The results showed that i.p. Semax had nootropic and analgesic actions. Dose-response characteristics were different for these different effects. Intranasal Semax was more effective in improving learning in animals than i.p. Semax but had no effect on pain sensitivity. Our results provide evidence that different mechanisms and brain structures are involved in mediating the nootropic and analgesic effects of Semax.

Effect of semax and its C-terminal peptide PGP on expression of neurotrophins and their receptors in rat brain during incomplete global ischemia

Neurotrophins regulate key functions of nervous tissue cells. Analysis of neurotrophin mRNA expression is an appropriate tool to assess therapeutic efficiency of antistroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide on mRNA expression of neurotrophins Ngf, Bdnf, and Nt-3 and their receptors TrkA, TrkB, TrkC, and p75 in rat frontal cortex, hippocampus, and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated at 30 min and 1, 2, 4, 8, 12, and 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our results demonstrated that ischemia caused a significant decrease in gene expression in the hippocampus. Semax and PGP treatment affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of neurotrophin receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides was observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the mechanism of Semax action and reveal certain features of mRNA expression of neurotrophins and their receptors under experimental conditions.

Semax increases erythrocyte deformability in the shearing blood stream in intact rats and rats with cerebral ischemia

208 Cerebral ischemia changes the rheological proper� ties of the blood, including the erythrocyte deform� ability (ED) (1). Its decrease may additionally aggra� vate brain microcirculation and worsen the pathologi� cal process. The synthetic drug Semax (ACTH4-7 - ProGlyPro), which has no hormonal properties, demonstrates neuroprotective effects during cerebral ischemia (2, 3). One of the mechanisms of the protec� tive action of Semax against brain ischemia is probably related to its influence on ED and, respectively, on the blood microcirculation. In this study, we examined in vitro the effects of Semax on ED in intact rats and rats with cerebral ischemia. Male Wistar rats weighing 210 ± 5 g were used for the study. In the first series of experiments, we studied the effects of Semax on ED in intact rats (n = 8). In the second series of experiments, we studied the effects of Semax on ED in rats with cerebral ischemia induced by simultaneous occlusion of the common carotid arteries performed under ether anesthesia (n = 8). For this purpose, the blood was sampled prior to and 90 min after the surgery. The blood was sampled from the jugular vein into test tubes containing 7% EDTA. The blood samples were divided into aliquots, which were mixed with a Semax solution with final concen� trations from 2 × 10 -9 to 2 × 10 -5 M or with a 0.9% NaCl solution, and incubated for 1 h. Then, these samples were diluted with a solution of polyethylenox� ide (MM = 5 × 10 6 ) at a ratio of 1 : 300 in order to get a suspension with a viscosity of 13 cP. We measured the ED in the shearing blood stream using a laser rota� tional diffractometer (7). The shear rate in the stream of erythrocyte suspension in the rheological gap of the diffractometer was changed by steps in the range from 13.8 to 1550 s

Effects of semax on the activity of carboxypeptidase H in brain regions and adrenal glands of rats

We studied the effects of a single semax administration to rats on the activity of carboxypeptidase H, a basic carboxypeptidase involved in the final stage of formation of biologically active peptides from their precursors. We found that the drug induced a long-term increase in the activity of carboxypeptidase, which lasted for 24 h. We believe that this change in the activity of the enzyme studied may serve as one of the factors that mediate semax action.

The Effect of Semax and Its C-End Peptide PGP on the Morphology and Proliferative Activity of Rat Brain Cells During Experimental Ischemia: A Pilot Study

The neuropeptide preparation Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has been employed successfully in clinical practice for treating patients with severe brain blood circulation disorders. In spite of numerous studies, many aspects of the therapeutic effects of this preparation remain unknown. In this context, the effects of Semax and its C-end tripeptide PGP on the functional morphology of nervous tissue cells were studied in the normal rat brain and in a model of incomplete global rat brain ischemia. In control animals, both peptides activated the capillary network and caused similar morphological changes to neurons and the neuropil regions. We show here for the first time at the histological level that Semax and PGP increased proliferation of the neuroglia, blood vessel endothelium, and progenitor cells in the subventricular zone. In these experimental conditions, only Semax abated the manifestation of ischemic damage to the nervous tissue. This was probably attributable to a decrease in vascular stasis symptoms as well as the trophic effect of the peptide.

Anticoagulation and Antiplatelet Effects of Semax under Conditions of Acute and Chronic Immobilization Stress

The effects of semax on anticoagulant, fibrinolytic, and platelet components of the anticoagulation system were studied on albino rats under conditions of acute and chronic immobilization stress. Semax exhibited a protective antistress effect after repeated intranasal administration under conditions of hypercoagulation developing in response to immobilization stress of different degree. The effect manifested in stimulation of the anticoagulation system.

10.1007/s11710-008-1009-1

The influence of a course of medical treatment with the Semax nootropic peptide (50 and 200 μg/kg) on alcohol motivation and general behavior was studied in rats preliminarily alcoholized over six months. Semax was also included in the scheme of complex therapy of human alcohol dependence in clinical practice. Experiments with rats showed an increase in the locomotor and exploratory activity of rats and a decrease in the degree of depressive-like components. This effect compensated the behavioral changes observed in the control group exposed to alcohol deprivation. At the same time, the behavior of test groups under anxiogenic conditions showed increased anxiety. Semax in a dose of 200 μg/kg caused a significant increase in alcohol motivation, whereas its lower dose induced no proalcohol effect. Clinical trials demonstrated the safety (the absence of side effects and fairly high tolerance) of Semax in the course of alleviating the acute withdrawal syndrome and its efficacy for the recovery of mnestic functions (which was similar to the efficacy of Pyracetam). Semax did not change the frequency of cases of pathological craving for alcohol, but increased the overall intensity of behavioral reactions, which made the craving for alcohol stronger. These results allowed determination of safe course doses of Semax (to 50 μg/kg) under conditions of chronic alcoholization and inclusion of this nootropic agent in a scheme of complex therapy for patients with alcohol dependence. The mechanisms underlying the individual differences in the effects of Semax should be studied further.