Pharmacology - Tryptamine nootropic

Discussion in 'Tryptamines' started by Rush, Apr 20, 2007.

  1. Rush

    Rush Titanium Member

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    Nov 30, 2006
    from switzerland
    Here is an interesting article i've found searching on the net
    as I am a fan of tryptamine familiy, and recently discovered 2C-D as nootropic in the phenetylamine familiy, is very happy in learning about this tryptamine memory enhancer.

    known with the code-name BGC20-761 or 5-methoxy-2-phenyl- N, N-dimethyltryptamine(2-Phen-5-Meo-N,N-DMT or 2P-5MEO-DMT or PMDT) for friends.

    BTW this infos are by now purely informative and curiosity purpose, as its unlikely(but who knows?) that it will ever touch the Research Chemical market.

    BGC20-761, a novel tryptamine analog, enhances memory consolidation and reverses scopolamine-induced memory deficit in social and visuospatial memory tasks through a 5-HT6 receptor-mediated mechanism by Ellen S. Mitchell; Blair J. Hoplight; Sean P. Lear; John F. Neumaier (pp. 412-420).

    Inhibition of 5-HT6 receptors has been shown to improve memory consolidation, thus we tested whether a novel tryptamine analog with high affinity for 5-HT6 receptors, BGC20-761 (5-methoxy-2-phenyl- N, N-dimethyltryptamine, PMDT), can enhance long-term memory. BGC20-761 (10mg/kg i.p.) alone had no effect on social recognition in young rats, however, at doses of 5mg/kg and 10mg/kg i.p, BGC20-761 dose-dependently reversed a deficit of social recognition induced by scopolamine (0.4mg/kg i.p.), an anticholinergic drug that impairs memory. BGC20-761 (10mg/kg i.p.), scopolamine (0.2mg/kg i.p.) or BGC20-761+scopolamine had no effects on novel object discrimination in young rats (2 months). In mature rats (6 months), recognition of the novel object was improved following administration of BGC20-761. Scopolamine had no effect in object recognition. However, the addition of scopolamine disrupted the memory-enhancing effect of BGC20-761. Based on the high affinity of BGC20-761 for 5-HT6 receptors, these cognitive enhancing effects are most likely mediated by 5-HT6 receptor inhibition. The difference in effects of BGC20-761 in young vs. mature rats may reflect the status of memory consolidation in these different age ranges.
    Keywords: Serotonin receptors; Memory; Aging; Novel object discrimination; 5-HT; 6

    a thing that shocked me is that just adding a phenyl group in second position changed a mind-blasting hallucinogen(5-meo-DMT obviusly) in a healty memory enhancer
    Last edited by a moderator: Sep 10, 2017
  2. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    Jan 14, 2003
    117 y/o from The Netherlands
    Maybe it didn't change it into anything, but just lost it's hallucinatory effects.
  3. Rush

    Rush Titanium Member

    Reputation Points:
    Nov 30, 2006
    from switzerland
    oh--- just found another one:​

    Ro4368554 - 3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole

    The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.

    Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.
    PMID: 15957009 [PubMed - indexed for MEDLINE]​

    here is memory versus happiness:
    Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test

    Systemically administered cholinomimetics or cholinesterase inhibitors can depress behavior in humans and animals, whereas antimuscarinic agents reverse this effect or even produce euphoria. Although these effects have been well documented, the specific brain regions that mediate them remain largely unknown. In the present experiments, muscarinic agonists and antagonists were locally injected into the nucleus accumbens of female Sprague-Dawley rats to test for their effects on behavioral depression in the Porsolt swim test and locomotor activity. Local, microinjections of the drugs in the accumbens elicited behaviors that were similar to the systemic effects reported in other studies. Injection of the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited swimming and escape behavior. This may be mediated in part by accumbens M1 receptors because blocking these receptors with the specific antagonist pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming. Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose-dependently decreased swimming. Two-way microdialysis suggested that this was in part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed M1/M2 receptor antagonist, also released ACh but did not decrease swimming, probably because the M1 receptors were blocked; the drug (1.0 microg) increased swimming time, much like pirenzepine. With the exception of arecoline, none of the drugs significantly affected locomotor activity in a photocell cage. Arecoline (40 microg), which had decreased swimming, reduced activity.The present study suggests that muscarinic receptors in the nucleus accumbens can control immobility in the Porsolt swim test. The onset of immobility may depend on the activation of post-synaptic M1 receptors. ​

    SB-271046 (SmithKline Beecham)

    SmithKline Beecham is developing the 5-HT6 antagonist, SB-271046, as a potential cognition enhancer. By December 1999, phase I trials had commenced [360354]. This drug was originally being developed primarily for the treatment of shizophrenia [284490], however, cognitive disorders, including but not limited to Alzheimer's disease, have been the main target since 1998 [394309]. SB-271046 is a potent, selective 5-HT6 antagonist with a pKi value of 8.9 [333710]. SB-258585, also known as 4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide is an analog of SB-271046 [322488]. Data recently presented at the Society for Neuroscience annual meeting in November 2000 demonstrated that administration of SB-271046 resulted in a signficant increase in glutamate and aspartate levels in the frontal cortex, without affecting noradrenaline, dopamine or 5-HT levels. This was stated to suggest that 5-HT6 antagonists might therefore be useful for treating cognitive dysfunction [390469]. The drug has also been radiolabeled in order to provide an assay for estimating in vivo 5-HT6 receptor occupancy [390470]. ​
    ---and i'm sorry if this topic becames off-section(more pharmacology) but i initially thought about tryptamines and im getting interested in this 5ht6 memory boosting---

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    Last edited by a moderator: Sep 10, 2017
  4. Richard_smoker

    Richard_smoker Gold Member

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    Sep 19, 2005
    from U.S.A.

    PERSONALLY, I think the MOST interesting aspect of these findings are the memory-enhancing effects on mature rats ONLY.

    The young, immature rats did NOT experience enhanced memory.

    The drug had no effect on young mice unless they had been pre-drugged with scopalamine.

    However, the older, mature rats DID experience improved memories.

    There are many interesting facts about the physical properties of young (pre-pubertal) brains, compared to the adult human brain. Current theory regarding neurological development during the human adolescent years involves literally trillions of nerves dying-off, as part of a normal process called "PRUNING."

    During our early development...there are 3 stages where the brain experiences neuronal "growth-spurts." These stages are when "EXUBERANT GROWTH" in neurons:
    1st: as a fetus, then,
    2nd: as a small child (0-3yrs old)
    3rd: child to about 13.

    During the neuronal growth period, the brain develops literally trillions of "extra" neurons...this probably provides for our "infinite potential"--the ability to learn several languages (or, in most of our cases, just to learn 1 language) is a giant undertaking.

    think about it...learning all about the physical, emotional, social, cultural, & meta-physical properties of the world around us is a huge undertaking, as is learning to control our bodies and interact with the physical world...especially if you believe that the starting material is more-or-less a "blank slate"...

    From age 13--throughout adolescence--to age 25, the brain goes thru PRUNING...getting rid of unnecessary neurons (potential pathways) and actual nerve cells DIE in this process of "maturing" the brain.

    Here is part of a layman-audience presentation called, The Adolescent Brain: A Work in Progress, by Pat Wolfe for ASCD (some kinda teacher's convention). I've edited the material somewhat by PRUNING her talk... BTW, if you're interested in learning neuroloscience, this talk is a GREAT starting point, available at the website quoted. I think most of us are somewhat curious about our brains & neuroscience...(or maybe we just care about "Research CHEMICALS"...).

    So, I wonder how this information applies to these rat brain findings?

    The research states that this 2P-5MEO-DMT MAY help the adult brain to function like the child brain in forming & consolidating memories...

    at any rate, it's interesting food for thought...and maybe the 2P-5MEO-DMT is interesting food for thought as well...

    Last edited by a moderator: Apr 30, 2017