Semax

Effects measured: Adding Semax to standard intensive therapy increased the rate of regression of general cerebral and focal, especially motor, deficits versus controls. Changes were tracked with clinical rating scales, EEG mapping, and somatosensory evoked potentials. This was a small non-randomized comparison and the abstract reports directional improvement rather than effect sizes with confidence intervals.

Side effects: No adverse events reported in this study

Sources: Gusev EI, Skvortsova VI, Miasoedov NF, et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34.

Effects measured: A single intranasal dose produced about a 1.4-fold increase in BDNF protein, a 1.6-fold increase in trkB tyrosine phosphorylation, an about 3-fold increase in exon III BDNF mRNA, and an about 2-fold increase in trkB mRNA in the hippocampus. Behaviorally, treated rats showed a distinct increase in the number of conditioned avoidance reactions.

Side effects: No adverse events reported in this study

Sources: Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60.

Effects measured: Both 50 and 250 microg/kg produced a rapid rise in BDNF protein in the basal forebrain at 3 hours, but not in the cerebellum, indicating region specificity. Semax bound specifically to brain cell membranes with a dissociation constant (Kd) of about 2.4 nM and stimulated BDNF synthesis in astrocytes, linking its cognitive effects to elevated basal-forebrain BDNF.

Side effects: No adverse events reported in this study

Sources: Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97(Suppl 1):82-86.

Effects measured: Semax produced a pronounced neuroprotective and antiamnesic effect: it decreased the volume of cortical infarction and improved both retention and performance of a conditioned passive-avoidance response versus untreated ischemic rats. The abstract reports the direction of effect rather than exact percentage reductions.

Side effects: No adverse events reported in this study

Sources: Romanova GA, Silachev DN, Shakova FM, et al. Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex. Bull Exp Biol Med. 2006;142(6):663-666.

Effects measured: Semax reversed or substantially attenuated stress-induced anhedonia, body-weight-gain suppression, adrenal hypertrophy, and the stress-induced drop in hippocampal BDNF. It had no significant effect in the forced swim test, so the antidepressant-like signal was specific to anhedonia and BDNF measures rather than all behavioral readouts.

Side effects: No adverse events reported in this study

Sources: Inozemtseva LS, Yatsenko KA, Glazova NYu, et al. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress. Eur J Pharmacol. 2024;983:176999.

Effects measured: Semax increased survival of cholinergic basal forebrain neurons about 1.5 to 1.7-fold versus control. At 100 nM it stimulated choline acetyltransferase activity in dissociated basal forebrain cultures. Across 1 nM to 10 microM it did not affect GABAergic neurons or glial-cell proliferation, indicating a selective effect on cholinergic neurons.

Side effects: No adverse events reported in this study

Sources: Grivennikov IA, Dolotov OV, Zolotarev YA, et al. Effects of behaviorally active ACTH (4-10) analogue - Semax on rat basal forebrain cholinergic neurons. Restor Neurol Neurosci. 2008;26(1):35-43.