RESUMO
Objective. To study the efficacy and tolerability of the new anxyolytic peptide selank in comparison with phenazepam. Material and methods. A comparative study of the anxiolytic effect and tolerability of selank and phenazepam was carried out in 60 patients with phobic-anxiety- and somatoform disorders (F40.2-9, F41.1-9, F45.0-1 by ICD-10) were examined. Results Pronounced anxiolytic and mild nootropic effects of selank were demonstrated. The anxiolytic effect lasted for a week after last receiving the peptide. Selank had a positive impact on the quality of life of the patients. Conclusion. The data obtained in the study extend therapeutic possibilities in the treatment of anxiety disorders.
Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Oligopeptídeos/uso terapêutico , Adolescente , Adulto , Ansiolíticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , Adulto JovemRESUMO
The influence two original derivatives of a therapeutically important peptide, bearing arachidonic acid residue with semax and proglyprol, upon platelet aggregation have been studied in vitro. It is established that both derivatives, in contrast to the parent peptide, possess moderate anti-aggregant properties and produce a dose-dependent decrease in the interplatelet interaction induced by ADP, epinephrine, and arachidonic acid within the concentration range of 0.018 - 1.8 mM. This activity was more pronounced for arachidonoylsemax in comparison with arachidonoylproglyprol.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Ácido Araquidônico/química , Fármacos Neuroprotetores/síntese química , Oligopeptídeos/síntese química , Fragmentos de Peptídeos/síntese química , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Prolina/análogos & derivados , Difosfato de Adenosina/farmacologia , Hormônio Adrenocorticotrópico/síntese química , Hormônio Adrenocorticotrópico/farmacologia , Ácido Araquidônico/farmacologia , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Células Cultivadas , Desenho de Fármacos , Epinefrina/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Prolina/síntese química , Prolina/farmacologia , Relação Estrutura-AtividadeRESUMO
The aim of this work was to study the delayed effects of chronic neonatal administration of the selective serotonin reuptake inhibitor fluvoxamine (FA) to white rat pups and to estimate the possibility to correct these effects by treatment with semax. Fluvoxamine was injected intraperitoneally at a dose of 10 mg/kg from postnatal days 1 to 14, and semax was injected intranasally at a dose of 0.05 mg/kg from postnatal days 15 to 28. It was shown that neonatal FA administration produced a significant delay in animal somatic growth. A loss in body weight was detected both during FA administration and 4-6 weeks after the last injection. Furthermore, FA administration increased the anxiety level and disturbed the learning ability of animals. The negative consequences of neonatal FA administration were largely compensated by Semax.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Ansiedade/patologia , Feminino , Fluvoxamina/toxicidade , Masculino , Ratos , Inibidores Seletivos de Recaptação de Serotonina/toxicidadeRESUMO
Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as C-terminal fragment for peptide drugs Semax and Selank. In recent years the independent effects of PGP were observed. The question was raised, whether PGP contributes to the effects ofpeptide drugs containing PGP as a fragment. The genome-wide analysis was performed to investigate the influence of PGP on the transcriptome of ischemic rat brain cortex tissues. The gene expression alterations caused by the action of the tripeptide PGP were compared with the gene expression of the control group "ischemia" at 3 and 24 h after permanent occlusion of left middle cerebral artery. The altered expression was detected for 29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety of functions: cytokines, transport proteins, transcription factors, transmembrane receptors, etc. Biological processes, which are related to the genes with altered expression, were distinguished. The influence of PGP on the diversity of biological processes in different systems of the organism is demonstrated for the first time. The process "Immune response" was the most statistically notable at 24 h after occlusion. The expression of the immune system genes was predominately down regulated.
Assuntos
Isquemia Encefálica/genética , Transtornos Cerebrovasculares/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/farmacologia , Prolina/análogos & derivados , Transcriptoma , Animais , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Transtornos Cerebrovasculares/imunologia , Transtornos Cerebrovasculares/patologia , Citocinas/genética , Citocinas/imunologia , Perfilação da Expressão Gênica , Imunidade Inata/efeitos dos fármacos , Masculino , Prolina/farmacologia , Ratos , Ratos Wistar , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologiaRESUMO
It has been established that fivefold intranasal administration of the peptide Leu-Pro-Gly-Pro (1 mg/kg) to rats with developing refractory hyperglycemia leads to restoration and normalization of the functions of anticoagulation and insular systems. In the blood of experimental animals, there was a decrease in the sugar level and platelet aggregation and an increase in anticoagulant and all kinds of fibrinolytic (total, enzymatic, non-enzymatic, Hageman-dependent) activity.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Peptídeos/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Anticoagulantes/administração & dosagem , Glicemia/efeitos dos fármacos , Agregação Celular/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/patologia , RatosRESUMO
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.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Prolina/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/biossíntese , Hormônio Adrenocorticotrópico/farmacologia , Animais , Encéfalo/patologia , Isquemia Encefálica/patologia , Masculino , Prolina/farmacologia , Ratos , Ratos WistarRESUMO
Proteolysis of Pro-Gly-Pro-Leu, Pro-Gly-Pro-Gly and Pro-Gly-Pro were studied comparatively to Met-Glu-His-Phe-Pro-Gly-Pro (semax). It is shown that all three peptides are considerably more stable to proteolysis by N-leucine-aminopeptidase (EC 3.4.11.1, Sigma, type VI, 9.2 units/mg), and by enzymes of nasal slime, brain microsomal fractions, and rat blood. Metabolites of the proteolysis showed that semax derives His-Phe-Pro-Gly-Pro only, Pro-Gly-Pro-Leu forms Gly-Pro-Leu, Pro-Gly-Pro and Gly-Pro, Pro-Gly-Pro-Gly gives Pro-Gly-Pro and Gly-Pro, and Pro-Gly-Pro forms Gly-Pro.
Assuntos
Glicina/química , Peptídeos/química , Prolina/química , Proteólise , Animais , Encéfalo/enzimologia , Enzimas/sangue , Leucil Aminopeptidase/química , RatosRESUMO
Semax effects on formation of active avoidance reaction in rats in different experimental models have been studied. It was shown that intraperitoneal Semax administration at a dose of 0.05 mg/kg accelerated acquisition of one-way active avoidance response when rats were trained to avoid electric foot-shock by jumping on the shelf. When rats were trained in shuttle-box the peptide increased the electroshock threshold value required to provocation of rat moving in experimental box and delayed acquisition of two-way active avoidance response. At the same time Semax stimulated avoidance response restoration in shuttle-box after functional disturbances induced by acute modification of cause-effect and spatial relationships in experimental environment. Data obtained support nootropic properties of Semax.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Fragmentos de Peptídeos/administração & dosagem , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Aprendizagem da Esquiva/fisiologia , Eletrochoque , RatosRESUMO
In the present paper anticoagulant-fibrinolytic effects of the peptide Pro-Gly-Pro-Leu in rats (370-500 g body weight) who consumed fatty foods with excess of saturated fatty acids (wheat flour and bread--35%, sugar--10%, margarine hydrogenated fats, mayonnaise, cheese--35% and offals--10%, cholesterol--1%, dry food--9%) has been established. The duration of the animals on the diet was 15 days. The experimental animals intranasally obtained peptide (200 microg/kg body weight per volume of 0.02 ml per 200 g body weight) 11 times (daily except weekends). Animals from the control group intranasally received instead of peptide its vehicle (0.85% solution of NaCl) at the same time and in the same amount. It has been shown that daily nasal administration of the regulatory tetrapeptide under fatty food intake for the entire period of the experiment has a positive effect on lipid metabolism. It warned the development of alimentary hypercholesterolemia, an increase in body weight, normalized disturbed lipid profile, blood cholesterol level. In addition, its administration also restored functional status of anticoagulation system and decreased elevated degree of blood coagulation to normal values. Possible mechanism of hypocholesterolemic activity of peptide can be explained by its ability to interact with receptors of blood or brain cells, and through a series of reactions mediated to reduce blood cholesterol levels. Thanks to the anti-platelet activity glyprolines effectively improves endothelial function and reduces the risk of blood clots in the blood vessels, providing improved rheological properties of blood and preventing the formation of atherosclerotic plaques in the arterial wall.
Assuntos
Anticolesterolemiantes/uso terapêutico , Colesterol/sangue , Gorduras na Dieta/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Administração Intranasal , Animais , Anticolesterolemiantes/administração & dosagem , Glicemia/metabolismo , Modelos Animais de Doenças , Hemostasia/efeitos dos fármacos , Hipercolesterolemia/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Resultado do TratamentoRESUMO
Based on the database information (literature period 1970-2010 gg.) on the effects of regulatory peptides (RP) and non-peptide neurotransmitters (dopamine, serotonin, norepi-nephrine, acetylcholine) it was analyzed of possible cascade processes of endogenous regulators. It was found that the entire continuum of RP and mediators is a chaotic soup of the ordered three-level compartments. Such a dynamic functional hierarchy of endogenous regulators allows to create start-up and corrective tasks for a variety of physiological functions. Some examples of static and dynamic patterns of induction processes of RP and mediators (that regulate the states of anxiety, depression, learning and memory, feeding behavior, reproductive processes, etc.) are considered.
Assuntos
Bases de Dados Factuais , Terapia de Alvo Molecular , Neurotransmissores , Peptídeos , Ansiedade/fisiopatologia , Humanos , Aprendizagem/fisiologia , Memória/fisiologia , Neurotransmissores/química , Neurotransmissores/classificação , Neurotransmissores/metabolismo , Peptídeos/química , Peptídeos/classificação , Peptídeos/metabolismo , Biologia de SistemasRESUMO
Heparin was bound to the arginine-containing peptide Arg-Pro-Gly-Pro with the molar ratio of heparin to the peptide 1:1. The complex compound showed antiplatelet, anticoagulative, and fibrin-depolymerization activities. In an in vivo study, in type 2 diabetes progression, a 5-fold intranasal administration of the compound restored both impaired insular and anticlotting functions in rats. Furthermore, blood fibrinolytic and anticoagulative activities increased.
Assuntos
Anticoagulantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Heparina/farmacologia , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Administração Intranasal , Animais , Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Hiperglicemia/induzido quimicamente , Masculino , Peptídeos/administração & dosagem , Ratos , Terapia TrombolíticaRESUMO
Proteolysis of semax (Met-Glu-His-Phe-Pro-Gly-Pro, Sem) and its analogues ([Ala1]Sem, [Gly1]Sem, [Thr1]Sem, [Trp1]Sem) that are differ from semax in substitution of N-terminal Met residue were studied. It is shown that such replacement changes the rate of peptides degradation by N-aminopeptidases (EC 3.4.11.2, Sigma, Type VI, 9.2 units. Akt. / mg). [Ala1]Sem, [Gly1]Sem and [Thr1]Sem semax analogues proved to be more stable to proteolysis than semax (Sem), and their initial product of proteolysis is His-Phe-Pro-Gly-Pro (Sem-5). For triptophan analogue both Glu-His-Phe-Pro-Gly-Pro (Sem-6) and Sem-5 product are formed in similar quantities. It is found that all investigated analogues can be used as inhibitors in Sem proteolysis.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Aminoácidos/química , Antígenos CD13/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Proteólise , Hormônio Adrenocorticotrópico/química , Hormônio Adrenocorticotrópico/metabolismo , Aminoácidos/metabolismo , Animais , Química Encefálica , Antígenos CD13/química , Membranas/química , Peptídeos/química , Ratos , Ratos WistarRESUMO
A study of the immunomodulating effect of selank showed that the total peptide and its fragment significantly change the expression of the genes for chemokines, cytokines, and their receptors in mouse spleen 6 and 24 h after administration of a single dose. Changes in the mRNA level of the majority of the genes under study were similarly observed after the administration of Gly-Pro, which was earlier identified as a selank pharmacophor, a minimum fragment with anitiviral activity. Pharmacological preparations based on endogenous regulatory peptides are studied intensely because they are the most promising class of drugs and have almost no side effects. The class includes selank, which is a synthetic analog of taftsin. Selank exerts anxiolytic and nootropic effects and, on the other hand, has pronounced antiviral properties.
Assuntos
Ansiolíticos/farmacologia , Antivirais/farmacologia , Quimiocinas/genética , Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Nootrópicos/farmacologia , Oligopeptídeos/farmacologia , Animais , Ansiolíticos/química , Antivirais/química , Fatores Imunológicos/química , Camundongos , Nootrópicos/química , Oligopeptídeos/química , RNA Mensageiro/genética , Receptores de Citocinas/genética , Tuftsina/química , Tuftsina/farmacologiaRESUMO
According to published data, peptide neurotensin is considered as endogenous antipsychotic agent. A series of oligopeptides have been synthesized based on the proposed active center of neurotensin. These oligopeptides (called neurotensin-like peptides, NLPs) have been studied on behavioral models, in which the functional state of the dopamine system of animals was modified by apomorphine injections. The results of verticalization, stereotypy, and yawning tests revealed NLPs that behave as antagonists of dopamine receptors. Radioligand analysis showed that these peptides compete for specific binding to these receptors with sulpiride, which is a D2-type selective antagonist of dopamine receptors. The high degree of NLPs efficiency manifested in the behavioral tests and radioligand analysis suggests that the their antipsychotic action can be mediated by dopamine receptors.
Assuntos
Antipsicóticos/administração & dosagem , Neurotensina/administração & dosagem , Oligopeptídeos/administração & dosagem , Transtornos Psicóticos/tratamento farmacológico , Receptores Dopaminérgicos/metabolismo , Animais , Animais não Endogâmicos , Antipsicóticos/síntese química , Antipsicóticos/uso terapêutico , Apomorfina/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Dopamina/metabolismo , Agonistas de Dopamina/metabolismo , Antagonistas de Dopamina/metabolismo , Masculino , Camundongos , Neurotensina/síntese química , Neurotensina/uso terapêutico , Oligopeptídeos/síntese química , Oligopeptídeos/uso terapêutico , Ensaio Radioligante , Ratos , Comportamento Estereotipado/efeitos dos fármacos , Comportamento Estereotipado/fisiologia , Sulpirida/administração & dosagem , Bocejo/efeitos dos fármacosRESUMO
Neurotrophins regulate key function of nervous tissue cells. Analysis of neurotrophins mRNA expression is an appropriate tool to assess therapeutic efficiency of the anti-stroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide upon mRNAs expression of neurotrophins Ngf, Bdrf, Nt-3 and their receptors TrkA, TrkB, TrkC, p75 in rat frontal lobes, hippocampus and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our showed that ischemia causes a significant decrease in gene expression in the hippocampus. Semax and PGP 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 receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides has been 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 semax mechanism of and present certain features of mRNA's expression of neurotrophins and their receptors in experimental conditions.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Isquemia Encefálica/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fatores de Crescimento Neural/genética , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Prolina/análogos & derivados , Hormônio Adrenocorticotrópico/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Masculino , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Prolina/farmacologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor de Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Receptor trkC/genética , Receptor trkC/metabolismoRESUMO
We discovered that simple proline-containing peptides Gly-Pro, Pro-Gly, Pro-Gly-Pro, and semax had an antistress protective effect on the organism appearing as anticoagulation system activation. Repeated intranasal injection of each of these peptides to rats prior to acute immobilization stress prevented a hypercoagulation response to prolonged stress lasting 60 min. At the same time there was increase of antithrombotic, anticoagulant, and fibrin depolymerization activity and recovery of enzymatic fibrinolytic activity. Dipeptides were found to have the greatest antistress effect. Our results showed that semax had a protective effect against enhanced blood coagulability resulting from repeated immobilization stress.
Assuntos
Fibrinolíticos/farmacologia , Oligopeptídeos/farmacologia , Prolina/química , Estresse Psicológico/prevenção & controle , Hormônio Adrenocorticotrópico/análogos & derivados , Hormônio Adrenocorticotrópico/farmacologia , Animais , Dipeptídeos/farmacologia , Imobilização , Masculino , Oligopeptídeos/química , Fragmentos de Peptídeos/farmacologia , Prolina/análogos & derivados , Prolina/farmacologia , Ratos , Estresse Psicológico/sangueRESUMO
Repeated (over 7 days) intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals at a dose of 1 mg/kg before injection of the diabetogenic metabolite alloxan provided effective protection of an organism against development of insulin-dependent diabetes mellitus and prevented development of hypercoagulating alterations in the system of hemostasis. An increasing in the anticoagulating and fibrinolytic activities in rat blood plasma was detected. The peptide under study also showed antidiabetogenic action: repeated intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals for 7 days inhibited development of diabetes symptoms in rats pretreated with alloxan.
Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Fibrinolíticos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Oligopeptídeos/uso terapêutico , Administração Intranasal , Aloxano , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Fatores de TempoRESUMO
1,2-Tritium-labeled 3-(O-carboxypropyl)- and 3-(O-carbomethoxypropyl)-oximes of 6alpha-methyl-16alpha,17alpha-cyclohexanopregn-4-ene-3,20-diones were obtained by the homogeneous catalytic hydrogenation of 1,2-dehydroprecursors with gaseous tritium and the subsequent separation of the resulting mixtures by HPLC. The specific radioactivities of 50-55 Ci/mmol were prepared using tris-(triphenylphosphine)-rhodium chloride.
Assuntos
Oximas/síntese química , Pregnenodionas/síntese química , Catálise , Marcação por Isótopo , Compostos Organometálicos , Compostos Organofosforados , Oximas/química , Pregnenodionas/química , TrítioRESUMO
The effects of the adrenocorticotropic hormone (ACTH(4-10)) analog, Semax (MEHFPGP), on the level of anxiety and depression in white rats have been studied in the normal state and against the background of cholecystokinin-tetrapeptide (CCK-4) action. Semax was injected intranasally in doses of 50 and 500 microg/kg 15 min before the testing. CCK-4 was administered intraperitoneally in a dose of 400 microg/kg 40 min before the testing. The level of anxiety was estimated in the elevated plus-maze test, and the degree of depression, in the forced swimming test. Semax administration did not influence the emotional state of animals in the normal state. The CCK-4 injection led to an increase in anxiety and depression in rats. Semax normalized the animal behavior disturbed by the CCK-4 administration, which attests to its anxiolytic and antidepressant effects at elevated levels of anxiety and depression.
Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Ansiolíticos/farmacologia , Ansiedade/fisiopatologia , Colecistocinina/farmacologia , Depressão/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , NataçãoRESUMO
Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.