Ketamine salts solubility

[S.J.B.]

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Design, Synthesis, and Evaluation of Analogues with Improved Potency and G-protein Activation Bias at the μ-Opioid Receptor
Corresponding author: Thomas E. Prisinzano (Department of Medicinal Chemistry, School of Pharmacy, University of Kansas, Lawrence, United States)
ACS Chemical Neuroscience 2020, Volume 11, Issue 12, Pages 1781–1790
Published online May 8th, 2020
https://doi.org/10.1021/acschemneuro.0c00191

Previous structure–activity relationship (SAR) studies identified the first centrally acting, non-nitrogenous μ-opioid receptor (MOR) agonist, kurkinorin (1), derived from salvinorin A. In an effort to further probe the physiological effects induced upon activation of MORs with this nonmorphine scaffold, a variety of analogues were synthesized and evaluated in vitro for their ability to activate G-proteins and recruit β-arrestin-2 upon MOR activation. Through these studies, compounds that are potent agonists at MORs and either biased toward β-arrestin-2 recruitment or biased toward G-protein activation have been identified. One such compound, 25, has potent activity and selectivity at the MOR over KOR with bias for G-protein activation. Impressively, 25 is over 100× more potent than morphine and over 5× more potent than fentanyl in vitro and elicits antinociception with limited tolerance development in vivo. This is especially significant given that 25 lacks a basic nitrogen and other ionizable groups present in other opioid ligand classes.

 

[S.J.B.]

Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats
Corresponding author: Richard A. Glennon (Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, United States)
ACS Chemical Neuroscience 2020, Volume 11, Issue 12, Pages 1762–1769
Published online May 1st, 2020
https://doi.org/10.1021/acschemneuro.9b00617

Methcathinone (MCAT; 1), the progenitor of numerous and widely abused “synthetic cathinone” central stimulants, exists as a pair of optical isomers. Although S(−)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(−)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.

Not surprisingly, alpha-des-methyl MCAT is significantly less potent as an in vitro dopamine and serotonin releaser than either of the MCAT enantiomers, although it is a roughly-equivalent norepinephrine releaser. It was also over 10 times less potent than either MCAT enantiomer in a rat self-stimulation study. However, alpha-methyl MCAT looks like it has potential. It was half as potent as racemic MCAT at DAT but twice as potent at SERT (although all compounds were only weakly active at SERT relative to DAT and NET) and had essentially identical potency to MCAT in the rat self-stimulation study.

 

[Rectify]

RALPH, The Cat
6-methoxyindole-3-yl 1-methylpiperidin-4-yl ether

FIDGET, The Dog
6-methoxyindole-3-yl piperidin-4-yl ether

FELIX, Da House Cat
6-methylthioindole-3-yl piperidin-4-yl ether

MUFFIN, The Cat
6-methylthioindole-3-yl 1-methyl-piperidin-4-yl ether

FADDEUS
6-methylthioindole-3-yl 1-methyl-piperidin-4-yl thioether

 

[Rectify]

ATLAS_T
6-methylthioindole-3-yl piperidin-4-yl thioether

FLO
piperidin-4-yl 3-chlorophenyl thioether

 

[Gaffy]

These sulfur compounds aren't very active to say the least..

 

[JoEhJoEh]

You answered me with this site? I had a real serious question, but if you don't want to have a good customer that nothing tells to others, okay...
Let it be
let it be
let it be
let it be
whisper words of wisdom
let it be

 

[Rectify]

Gaffy,

Thanks for the 411 with respect to sulfur.

 

[Rectify]

KAREN
1-(4-bromophenyl)-2-propylaminopropane

 

[Gaffy]

Gaffy,

Thanks for the 411 with respect to sulfur.

Always ready to help!
If you have any doubt about the activity of a compound just enter it in swisstargetprediction.ch

 

[Gaffy]

NIPP

N-Isopropyl-Pentedrone

My favorite, more euphoria than Hexen, and a real rarity.

 

[Rectify]

CHASING_AMY
1-(3-methoxy-4-amylphenyl)-2-aminopropane

 

[Gaffy]

FUNKY DUST

SPRINKLE SLEEP

 

[Rectify]

AMY_T
1-(5-amylindole-3-yl)-2-dimethylaminoethane

 

[polymath]

Oleic acid causes sedation and motor incoordination similar to diazepam.

Oleic Acid Produces Motor Incoordination and Hypoactivity in Infant Wistar Rats Through GABA_A Receptors

A mixture of eight fatty acids (linoleic, oleic, palmitic, stearic, myristic, elaidic, lauric, and palmitoleic acids) at similar concentrations that have been identified in human amniotic fluid exerts anxiolytic-like effects similar to diazepam in adult Wistar rats through actions at...

www.sciencepublishinggroup.com

 

[Rectify]

HEYZEUS
1-(4-methoxyphenyl)-3-(1-piperidinyl)butane

 

[Gaffy]

HOMO DEUS

HOMO DEUS DEUS

active (very strong pbblty) at
Sigma, Sert, Dat, Vesicular Amine Transporter, D2, NET, Mu, Kappa, Delta, NMDA, adrenergic, acetylcholine, etc.

VIVENDUM

 

[Rectify]

WITTIG
1-(6-methylindole-yl)-2-dimethylaminoethane

WERNER
1-(6-methylindole-yl)-2-aminopropane

 

[Gaffy]

A patent about phenylpiperidines in which my rediscovery MEPHOZINE appears, with synthesis

Patent Public Search | USPTO

appft.uspto.gov

 

[Rectify]

NSAID
4-chloro-N-acetylaniline

HANNAH palindrone HANNAH
1,4-bis(2-aminoethyl)-2,5-dimethoxybenzene

AMADEUS
1,4-bis(2-aminopropyl)benzene

 

[Rectify]