acth-(4-7)--pro-gly-pro- and Amnesia

A new mixture of tripeptides (NMT: H-Lys-Asp-Glu-OH, H-Asp-Glu-Pro-OH, H-Asp-Glu-Arg-OH) in doses of 150 and 300 mg/kg per day produces clearly pronounced neuroprotective effect in rats with brain ischemia and decreases neurologic deficiency 1.1 times more effectively than reference drug semax. NMT (10, 50 and 150 mg/kg) had marked antihypoxic effect on mice in hermetic and altitude chamber. NMT in doses of 10 and 50 mg/kg was more effective than semax in hermetic chamber (1.3 and 1.5 times, respectively) and in a dose of 150 mg/kg in altitude chamber (1.9 times). NMT (50 and 150 mg/kg) had also marked antiamnesic effect on model amnesia caused by scopolamine in rats and was more effective (1.5 and 1.4 times, respectively) than semax in equal doses. NMT (50 and 150 mg/kg) also had marked antiamnesic effect on model amnesia caused by maximal electroshock and complex extreme factors in mice and in both doses was 4 times more effective than semax on the first model and in a dose of 150 mg/kg was 2.9 times more effective on the second model. NMT (50 mg/kg) increased the amplitude of transcallosal evoked potential in rat brain by 69% and was more effective than semax in equal dose. Thus, NMT is a promising neurotropic drug with neuroprotective, antihypoxic and antiamnesic activity.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Brain Ischemia; Electroshock; Evoked Potentials, Motor; Hypoxia; Male; Mice; Neuroprotective Agents; Nootropic Agents; Oligopeptides; Peptide Fragments; Rats; Scopolamine

Upon single administration, mexidol and semax only in doses of 100 and 0.05 mg/kg, respectively, produced an antihypoxic effect on mice in the altitude chamber and hermetic chamber tests. Preventive course administration of mexidol and semax for 6 days gave significant antihypoxic effect on the model of acute hypobaric hypoxia in mice in doses of 75 and 0.1 mg/kg per day, respectively, in which the same preparations upon single administration were ineffective. Neither mexidol nor semax upon single administration were effective on the models of acute hemic and histotoxic hypoxia. On various models of amnesia (except that induced by the maximal electroshock) in mice, both mexidol and semax exhibited marked antiamnesic effects comparable with that of the reference nootrope drugs piracetam and oxyracetam. Mexidol showed a linear, while semax exhibited a bell-shaped reversible dose-effect relationships. Mexidol and semax inhibited the ortho- and antidromic population response spikes of CA1 pyramidal neurons of survival hippocampal slices in rats. It was estimated that mexidol (in contrast to semax) increased oxygen consumption in rat brain mitochondria and had a linear dose-effect relationship in a concentration range of 1-5 mM. It is concluded that mexidol should be used in high doses (for both single and course administration) for obtaining antihypoxic and antiamnesic effects, while semax requires a thoroughly controlled choice of dosage.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Hypoxia; Mice; Mitochondria; Neuroprotective Agents; Oxygen Consumption; Peptide Fragments; Picolines; Psychotropic Drugs; Pyramidal Cells; Rats; Rats, Wistar; Time Factors

Semax had a pronounced neuroprotective and antiamnesic effect during focal photoinduced ischemia of the prefrontal cortex. Intranasal administration of Semax for 6 days decreased the volume of cortical infarction and improved retention and performance of conditioned passive avoidance response.

Topics: Administration, Intranasal; Adrenocorticotropic Hormone; Amnesia; Animals; Animals, Outbred Strains; Brain Infarction; Cerebral Cortex; Ischemic Attack, Transient; Male; Neuroprotective Agents; Peptide Fragments; Rats; Treatment Outcome