• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

Ketamine salts solubility

Status
Not open for further replies.
Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Parés, Salvador Fernández-Arroyo, Jorge Joven, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Joan Brunet, Alfons Nonell-Canals, Melchor Sanchez-Martinez and Javier A. Menendez
Front. Endocrinol., 06 November 2018 | https://doi.org/10.3389/fendo.2018.00657

Abstract

Metformin has been proposed to operate as an agonist of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that mimics most of the metabolic responses to calorie restriction. Herein, we present an in silico analysis focusing on the molecular docking and dynamic simulation of the putative interactions between metformin and SIRT1. Using eight different crystal structures of human SIRT1 protein, our computational approach was able to delineate the putative binding modes of metformin to several pockets inside and outside the central deacetylase catalytic domain. First, metformin was predicted to interact with the very same allosteric site occupied by resveratrol and other sirtuin-activating compounds (STATCs) at the amino-terminal activation domain of SIRT1. Second, metformin was predicted to interact with the NAD+ binding site in a manner slightly different to that of SIRT1 inhibitors containing an indole ring. Third, metformin was predicted to interact with the C-terminal regulatory segment of SIRT1 bound to the NAD+ hydrolysis product ADP-ribose, a “C-pocket”-related mechanism that appears to be essential for mechanism-based activation of SIRT1. Enzymatic assays confirmed that the net biochemical effect of metformin and other biguanides such as a phenformin was to improve the catalytic efficiency of SIRT1 operating in conditions of low NAD+ in vitro. Forthcoming studies should confirm the mechanistic relevance of our computational insights into how the putative binding modes of metformin to SIRT1 could explain its ability to operate as a direct SIRT1-activating compound. These findings might have important implications for understanding how metformin might confer health benefits via maintenance of SIRT1 activity during the aging process when NAD+ levels decline.
Click to expand...

This antidiabetic is known to increase the average lifespan of mice by a few %, even if they don't have any metabolic disease. Resveratrol, quinine and some other natural products are claimed to have the same SIRT1 effect.
 
polymath said:
Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Parés, Salvador Fernández-Arroyo, Jorge Joven, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Joan Brunet, Alfons Nonell-Canals, Melchor Sanchez-Martinez and Javier A. Menendez
Front. Endocrinol., 06 November 2018 | https://doi.org/10.3389/fendo.2018.00657



This antidiabetic is known to increase the average lifespan of mice by a few %, even if they don't have any metabolic disease. Resveratrol, quinine and some other natural products are claimed to have the same SIRT1 effect.
Click to expand...

Is there epidemiologic data showing increased lifespan in metformin patients?

Resveratrol is effectively a non-drug, and id gamble that quinine at sirt activating doses does bad things to the qt interval.
 
At least there is this: https://www.karger.com/Article/FullText/502257
If observational studies (cohort, case-control, and cross-sectional studies) are included and the onset or prevalence of “diseases of aging” (cancer, CVD, kidney failure, fracture, or cognitive impairment) is measured, the results suggest that diabetics taking metformin had a lower rate of all-cause mortality and of developing any cancer even compared to the general nondiabetic control population
Click to expand...

I also had the suspicion that resveratrol and ginseng extracts have inappropriate pharmacokinetics for use as a medicine. Ditto for the side effects of quinine.
 
1-phenyl-1-methoxy-2-aminoethane.png


BOPEA
BenzylOxyPhenylEthylAmine
1-phenyl-1-methoxy-2-aminoethane
 
Rectify said:
N-acetyl-4-chloroaniline.png


GAFFY
opsin/N-acetyl-4-chloroaniline
non steroidal pain reliever

Keep Your Friends Close And Your Enemies Closer.
Click to expand...
There already is a drug called Gaffy, it's Mephozine. But thanks for thé attention
 
4,5-dihydroimidazole-2-yl-naphthalene.png


NAPHAZOLINE eye drops
4,5-dihydroimidazole-2-yl-naphthalene

4,5-dihydroimidazole-2-yl-1,2,3,4-tetrahydronaphthalene.png


TETRAHYDROZOLINE eye drops
4,5-dihydroimidazole-2-yl-1,2,3,4-tetrahydronaphthalene

Gaffy,
I couldn't find Mephozine's chemical structure on Wikipedia or Google. Could you please draw it or at least give the IUPAC name? Enquiring minds want to know ! Thx, AMP.

opsin.ch.cam.ac.uk

1-(4,5-dihydroimidazole-2-yl)-1-phenyl-1-oxomethane.png


JACK
1-(4,5-dihydroimidazole-2-yl)-1-phenyl-1-oxomethane

1-(4,5-dihydroimidazole-2-yl)-1-(3,4-methylenedioxyphenyl)-1-oxomethane.png


JILL
1-(4,5-dihydroimidazole-2-yl)-1-(3,4-methylenedioxyphenyl)-1-oxomethane

1-cyclohexyl-2-ethylaminopropane.png


SHARON
1-cyclohexyl-2-ethylaminopropane

H-(C=O)-H
SHERM
formaldehyde
 
Last edited:
1-(2,6-dimethoxy-4-chlorophenyl)-2-aminopropane.png


CLAIRE
1-(2,6-dimethoxy-4-chlorophenyl)-2-aminopropane
Psi-DOC

1-(5-chloroindole-3-yl)-2-dimethylaminoethane.png


ELECTRO NATE
1-(5-chloroindole-3-yl)-2-dimethylaminoethane
 
1-(4-isopropylphenyl)-1-oxo-2-methylaminopropane.png


ASHLEY
1-(4-isopropylphenyl)-1-oxo-2-methylaminopropane

1-(4-isopropylphenyl)-2-ethylaminopropane.png


BONNIE
1-(4-isopropylphenyl)-2-ethylaminopropane

4-isopropylphenyl piperidine-4-yl ether.png


DOG IS MY COPILOT (DIMC)
4-isopropylphenyl piperidine-4-yl ether

Hawaii 5-oh!
 
Last edited:
v5aJLdyQjjOa_TnjFPrSvofJx2s_ky7rZ1aKRnW5YtAwnV5JW_7UG5_bAmiDwdUMlbDgmMzweLWCJgXP_uGH3S-_7DNiYNaWTklI9m8rGiliNwNL


Shady wants to kill me slowly with a spoon and watch the life fade out of my eyes.
G2-OH Polyamidoamine (PAMAM) dendrimer




am I doing this right?
 
SnafuInTheVoid said:
v5aJLdyQjjOa_TnjFPrSvofJx2s_ky7rZ1aKRnW5YtAwnV5JW_7UG5_bAmiDwdUMlbDgmMzweLWCJgXP_uGH3S-_7DNiYNaWTklI9m8rGiliNwNL


Shady wants to kill me slowly with a spoon and watch the life fade out of my eyes.
G2-OH Polyamidoamine (PAMAM) dendrimer




am I doing this right?
Click to expand...

Placing polymers or peptides here is perhaps cause for life-long ban i believe (you'll have to double check with subforum mods)
 
negrogesic said:
Placing polymers or peptides here is perhaps cause for life-long ban i believe (you'll have to double check with subforum mods)
Click to expand...
can't tell if serious or not?

:/

please don't ban me, really the last thing I need right now after being blacked out for a few days
 
Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase
Abir T. El‐Alfy, Ehab A. Abourashed, Christina Patel, Nunmoula Mazhari, HeaRe An, Andrew Jeon
https://doi.org/10.1111/jphp.13174

Abstract

Objectives
The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes.
Methods
Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC50). The most potent compound was investigated in the elevated plus maze (EPM) rodent anxiety model.
Key findings
Three compounds, licarin A (9), 5′‐methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 μm ± 2.02, 4.57 μm ± 0.66 and 38.29 μm ± 6.18, respectively. None of the purified compounds showed significant MAGL inhibition. Because of its relative high potency and selectivity, compound 8 was further evaluated in the EPM animal model of anxiety. The compound showed significant increase in number of open arm entries (P < 0.05) when administered at 120 mg/kg dose. No effect was observed on the locomotor activity.
Conclusions
Results collected introduce active nutmeg compounds as potential leads for further development. Of the three compounds, 8 possesses highest potency and FAAH selectivity as well as anxiolytic activity. Furthermore, in vivo testing in appropriate behavioural animal paradigms is warranted.
Click to expand...

Many have probably seen this before, but an interesting thing to note is that you can extract these phenolics with alkaline water while keeping the lipophilic components undissolved. Not sure if the IC50 values are low enough to be effective at reasonable doses, though.
 
3,5-dimethoxyphenyl piperidin-4-yl ether.png


HUILE DE FORTUNA (HDF)
3,5-dimethoxyphenyl piperidin-4-yl ether

3,5-dimethoxy-4-methylphenyl piperidin-4-yl ether.png


LILA
3,5-dimethoxy-4-methylphenyl piperidin-4-yl ether

3,5-dimethoxy-4-ethylphenyl piperidin-4-yl ether.png


SASHA
3,5-dimethoxy-4-ethylphenyl piperidin-4-yl ether
 
Last edited:
1-(5-oxo-4-azaindole-3-yl)-2-dimethylaminoethane.png


PATTY
1-(5-oxo-4-azaindole-3-yl)-2-dimethylaminoethane

1-(5-oxo-4-azaindole-3-yl)-2-aminopropane.png


JEB
1-(5-oxo-4-azaindole-3-yl)-2-aminopropane

piperidin-4-yl 3,5-dimethyl-4-methoxyphenyl ether.png


AZRAEL777
piperidin-4-yl 3,5-dimethyl-4-methoxyphenyl ether
 
Piperidine-4-yl-sulfinylbenzene.png


IRIS (SIRI backwards)
piperidine-4-yl-sulfinylbenzene

Piperidine-4-yl-sulfinyl-3,4-methylenedioxybenzene.png


CAPONE
piperidine-4-yl-sulfinyl-3,4-methylenedioxybenzene



I'll Fly Away.

1-(3-methoxy-4-butylthiophenyl)-2-aminopropane.png


GARGAMEL
1-(3-methoxy-4-butylthiophenyl)-2-aminopropane

1-cyclohexyl-2-propylaminopropane.png


PEE WEE
1-cyclohexyl-2-propylaminopropane

Ethyl Tricks Methyl. Propyl Tricks Ethyl. Butyl Tricks Propyl. And so forth.

There are methyl and ethyl, but butyl is futile.
 
Last edited:
µ-Opioid receptor–induced synaptic plasticity in dopamine neurons mediates the rewarding properties of anabolic androgenic steroids

  1. View ORCID ProfileLeonardo Bontempi1,* and
  2. View ORCID ProfileAntonello Bonci2,*
  3. 1Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
  4. 2Global Institutes on Addictions, Miami, FL 33132 USA.
  5. ↵*Corresponding author. Email: [email protected](L.B.); [email protected] (A.B.)
Hide authors and affiliations

Science Signaling 01 Sep 2020:
Vol. 13, Issue 647, eaba1169
DOI: 10.1126/scisignal.aba1169

Science | AAAS

stke.sciencemag.org stke.sciencemag.org

This probably explains some of the behavioral effects of anabolic steroids.

The experimental procedure was first to identify synaptic plasticity induction from nandrolone and testosterone. Then they administered an antagonist to the androgen receptor and observed plasticity occurring in the absence of androgen receptor activation. Next beta endorphin levels (in both plasma and vta) were measured by Elisa and found to be higher after administration of testosterone or nandrolone. Next mu opioid inhibiton was shown to block the synaptic plasticity. Finally vta specific injections of mu antagonists were demonstrated to be sufficient in inhibiting synaptic plasticity and conditioned place preference from steroids.
 
Status
Not open for further replies.
Top