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Comment · Fri, July 3, 2015 · Ceretropic

semax/selank and μ-opioid agonists (ie, tianeptine) report

Original post in this thread

nakedproof · 4 points

I've have a few bad experiences with semax(and others like na-semax-amidate), selank and μ-opioid agonists (tianeptine and tramadol specifically). I become very terse, aggressive and irritated with this combination.

I was surprised when I became agitated when I took tianeptine and semax together (12mg tianeptine and ~400mcg semax nasal spray), but thought I was just having an off day. I also had another experience with na-semax (may have been amidate, I dont remember) and 30mg of tianeptine which ended in me trying to drink the irritation away)

I also had an experience with about 12mg of tramadol and na-selank which resulted in the same sort of mental/emotional discomfort and irritation.

That's all, if anyone has had similar experiences or may have an explanation, feel free to comment

What they were answering

Direct reply to the original post — see the thread post above.

u/MisterYouAreSoDumb · Ceretropic

Both Semax and Selank inhibit the breakdown of endogenous opioids.

Semax and Selank Inhibit the Enkephalin-Degrading Enzymes of Human Serum

Dose-dependent effect of synthetic heptapeptides Semax (Met-Glu-His-Phe-Pro-Gly-Pro) and Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) on the enkephalin-degrading enzymes of human serum was demonstrated. The inhibitory effects of Semax (IC5010 μM) and Selank (IC5020 μM) are more pronounced than that of puromycin (IC5010 mM), bacitracin, and some other inhibitors of peptidases. Beside the heptapeptides, their pentapeptide fragments also possessed an inhibitory effect; tri-, tetra- and hexapeptide fragments did not display such an effect. As the above enzymes take part in degradation of not only enkephalins but also other regulatory peptides, it can be assumed that one of the mechanisms of biological activity of Semax and Selank is related to this inhibitory activity of theirs.

Also, Semax has been shown to decrease the analgesia from exogenous opioids.

ACTH \(4-10\) analogue Semax has analgetic activity and interact with opioid system.

The melanocortin and opioid systems have opposite activities, and have therefore been considered as functional antagonists. It has been reported that high concentrations of SEMAX antagonize MC4 and MC5 receptors in vivo and in vitro. The aim of the present work was to study the mechanisms of Semax influence on pain sensitivity and peptide interaction with opioid system. The present work was carrying out in white rats. Pain sensitivity was measured by using Randall-Selitto paw-withdrawal test and tail flick test. Semax was administered intraperitonealy at dose 0, 5 mg/kg. Semax reduced pain threshold in paw-withdrawal test and had no effect in tail flick test. To study the mechanisms of Semax analgetic effects we used naloxone (opioid receptors antagonist) and morphine (mu-opioid receptor agonist). Intraperitoneal pre-treatment with naloxone (1mg/kg, 15 min before peptide injection) failed to influence Semax analgesic effect, naloxone 5 mg/kg reduced Semax analgesia in paw-withdrawal test. Semax administration 15 min before morphine (5 mg/kg) decrease morphine effects in paw-withdrawal test and did not affected morphine analgesia in tail flick test. These data also suggest the melanocortin and opioid system interaction. We can suppose that Semax effects on nociception depend on the level of opioid system activity.

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