Ketamine salts solubility

[sekio]

Drug-induced acute psychosis in an adolescent first-time user of 4-HO-MET
Jakob Taljemark, Bjorn Axel Johansson
Eur Child Adolesc Psychiatry (2012) 21:527–528 DOI 10.1007/s00787-012-0282-9

4-HO-MET (4-hydroxy-N-methyl-ethyltryptamine), also known as metocin, is a synthetic hallucinogenic psychedelic drug. It resembles psilocin, the hallucinogenic component found in ‘‘magic mushrooms’’ [1]. In many countries including Sweden [2], 4-HO-MET has not yet been classified as an illicit substance, and can be ordered on the internet as a so-called ‘‘legal high’’. We describe a case where an adolescent presenting with apathy and mutism was later diagnosed with a drug-induced acute psychosis after inhalation of 4-HO-MET. ‘‘B’’, a 17-year-old boy living with his parents, was vadmitted to the acute medical department after being found by police, wandering along a motorway in his underwear. He expressed to the policemen that ‘‘I will not talk to anyone’’ and then remained mute and apathetic. [...] On admission, blood tests and a CT head scan were conducted, showing no significant abnormalities. A bedside urinary toxicology screen was positive for THC and cocaine, but no further analysis was done. ‘‘B’’ received supportive care. On the evening of admission, after being apathetic all day, he suddenly took his own discharge. He was soon found outside the hospital, having jumped 3–4 m from a roof. [...] On the day of discharge, 11 days after hospital admission, a mental state examination indicated no ongoing psychiatric illness, and ‘‘B’’ disclosed the entirety of his story. He had received 4-HO-MET powder from a friend who had ordered the drug over the internet. ‘‘B’’ inhaled approximately 100 mg of 4-HO-MET on the evening before admission. He soon started seeing doors in the bookcase in front of him. In panic he left the apartment. He walked the streets that he experienced as under a metre of water and filled with snakes. He felt distressed, lonely and persecuted. He sensed insects under his skin and his heart jumping out of the chest. ‘‘B’’ remembered being admitted to hospital and inside his head he heard his father’s voice repeating ‘‘you have never dared to dive’’. He therefore escaped from the ward, climbed onto a roof and ‘‘dived’’ to prove his father wrong.

So, uh, respect the mushroom. Or you'll be found wandering along a highway clad only in your skivvies, then throw yourself off a hospital roof.

Also, 100mg of psilocin or its analogs is too much.

 

[DotChem]

Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning.
Davis AK¹, Barsuglia JP², Windham-Herman AM³, Lynch M², Polanco M².
1Department of Psychiatry and Behavioral Sciences, Behavioral Pharmacology Research Unit, Johns Hopkins School of Medicine, Baltimore, MD, USA.2 Crossroads Treatment Center, Rosarito, Mexico.3 Yale School of Medicine, New Haven, CT, USA.

Abstract

Background and aims:
Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. Therefore, this study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning.

Methods:
Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Results:
Most participants (72 percent) had used opioids for at least 4 years and 69% reported daily use. Most (80.0% ) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25 percent)reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54 percent) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41% of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48% reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective well-being and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

Conclusion:
The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.


KEYWORDS:

effectiveness; heroin; ibogaine; outcomes; prescription opioids

 

[sekio]

 

[S.J.B.]

Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias
Corresponding author: Thomas D. Bannister (Department of Chemistry, The Scripps Research Institute, Jupiter, United States)
Journal of Medicinal Chemistry 2018, Volume 61, Issue 19, Pages 8895-8907
Published online September 10th, 2018
https://doi.org/10.1021/acs.jmedchem.8b01136

While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/βarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

NSFW:

 

[DotChem]

Ibogaine Acute Administration in Rats Promotes Wakefulness, Long-Lasting REM Sleep Suppression, and a Distinctive Motor Profile
Gonz?lez J1, Prieto JP2, Rodr?guez P3, Cavelli M1, Benedetto L1, Mondino A1, Pazos M3, Seoane G3, Carrera I3, Scorza C2, Torterolo P
Frontiers in Pharmacology. 2018 Apr 27;9:374. doi: 10.3389/fphar.2018.00374. eCollection 2018

ABSTRACT

Ibogaine is a potent psychedelic alkaloid that has been the focus of intense research because of its intriguing anti-addictive properties. According to anecdotic reports, ibogaine has been originally classified as an oneirogenic psychedelic; i.e., induces a dream-like cognitive activity while awake. However, the effects of ibogaine administration on wakefulness (W) and sleep have not been thoroughly assessed.The main aim of our study was to characterize the acute effects of ibogaine administration on W and sleep. For this purpose, polysomnographic recordings on chronically prepared rats were performed in the light phase during 6 h. Animals were treated with ibogaine (20 and 40 mg/kg) or vehicle, immediately before the beginning of the recordings. Furthermore, in order to evaluate associated motor behaviors during the W period, a different group of animals was tested for 2 h after ibogaine treatment on an open field with video-tracking software. Compared to control, animals treated with ibogaine showed an increase in time spent in W. This effect was accompanied by a decrease in slow wave sleep (SWS) and rapid-eye movements (REM) sleep time. REM sleep latency was significantly increased in animals treated with the higher ibogaine dose. While the effects on W and SWS were observed during the first 2 h of recordings, the decrement in REM sleep time was observed throughout the recording time. Accordingly, ibogaine treatment with the lower dose promoted an increase on locomotion, while tremor and flat body posture were observed only with the higher dose in a time-dependent manner. In contrast, head shake response, a behavior which has been associated in rats with the 5HT2A receptor activation by hallucinogens, was not modified. We conclude that ibogaine promotes a waking state that is accompanied by a robust and long-lasting REM sleep suppression.In addition, it produces a dose-dependent unusual motor profile along with other serotonin-related behaviors. Since ibogaine is metabolized to produce noribogaine, further experiments are needed to elucidate if the metabolite and/or the parent drug produced these effects.


KEYWORDS: REM sleep; hallucinogens; ibogaine; psychedelics; wakefulness

 

[Pomzazed]

I like Catrypt, does it MeO-w?

 

[Dresden]

Si, claro!

TRIPNOTIC

KRATOMANYL

You know I'm getting silly.
But not really.

SUPERB

-a so(m)ber MDA
-no mydriasis
-stimulating
-lasts 10 hours
-moderate hyperthermia
-music appreciation
-marked jaw clenching
-not sexual

If my brain turns into plastic in the next 2 or 3 weeks, then I'll be sure to let you know.

NEWTONIAN

-mellifluous
-inspired by jasmine

 

[S.J.B.]

Abuse Potential of Biased Mu Opioid Receptor Agonists
Corresponding author: S. Stevens Negus (Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States)
Trends in Pharmacological Sciences 2018, Volume 39, Issue 11, Pages 916-919
Published online October 18th, 2018
https://doi.org/10.1016/j.tips.2018.08.007

G protein-biased mu opioid receptor (GPB-MOR) agonists constitute an emerging class of opioid analgesics. The first-in-class GPB-MOR agonist TRV130 (oliceridine) produces typical opioid-like abuse-related effects in rodents and humans. Although GPB-MOR agonists may be safer than conventional opioids on some endpoints, prevailing evidence suggests that they will retain opioid-like abuse potential.

Remember oliceridine?

It was all over the news as an up-and-coming "low abuse potential" opioid, but it looks like both animal studies and a human trial indicate otherwise.

 

[S.J.B.]

Computer-Aided Studies for Novel Arylhydantoin 1,3,5-Triazine Derivatives as 5-HT6 Serotonin Receptor Ligands with Antidepressive-Like, Anxiolytic and Antiobesity Action In Vivo
Corresponding author: Jadwiga Handzlik (Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University, Cracow, Poland)
Molecules 2018, Volume 23, Issue 10, Page 2529
Published online October 3rd, 2018
https://doi.org/10.3390/molecules23102529

This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamine D2 receptors were evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT6 receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as "druglikeness" in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as the most active 5-HT6R agents within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, the most active one in the series (5-HT6R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6–197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds form with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro.

NSFW:

 

[sekio]

- probably a metabolite of pyrrolidinopentiophenone

 

[clubcard]

- probably a metabolite of pyrrolidinopentiophenone

Pyrophenidone is a bioisostere of pyrovalerone. The idiots making my designs couldn't spot the difference between a piperidine ring and a pyrrolidine ring for diphenidine. The latter turned out to be a stimulant so add a ketone... more potent... add a p-Me... wow, it's the same as pyrovalerone! A bit more potent due to LogP and importantly that methyl is a sacrificial moiety - you KNOW what the metabolites will be. I mean, we did check, but I'm very keen on checking metabolism. A useful fact...

 

[Pomzazed]

Add NO2 then.. for yellowness...

 

[clubcard]

Add NO2 then.. for yellowness...

Aromatic nitro groups often cause potentially dangerous metabolites. While the body is generally an oxidative instrument, reduction of aromatic nitro groups to amines is an issue. I specifically wanted that -CH3 to be readily oxidised. I don't design, run a full set of tests to check if something poses a threat. From day 1 I wanted to KNOW what the metabolites would be. Without the ketone it was mild, with the ketone it was quite potent but it took a long time to reach baseline but with the -CH3 added, it was reliable and repeatable that it lasts for 2 hours and drops off within another 2 hours.

Obviously people asked if it replaced cocaine. I am adamant that it was not. I deeply dislike cocaine because it funds terrorism in South America and all it does for me is make me feel annoyed with myself. Of course, I DID design a synthetic cocaine that is achiral and passed the taste test but all that would do is provide criminals with a way to circumvent the law which with the best will in the world, harms people. Pity because it was finding the right addition salt that took the most effort. One less hydrogen bond acceptor means you need something to push up the MP.... but the base was a liquid which pleased me - you can't rock it up!

 

[Dresden]

IONEXIA

For When You're Sick Of Designing Molecules, But Your Friend Is Not Ready To Leave The Lieberry Yet.

Here is his mix that he was making: https://soundcloud.com/syn_aesthetik/ionexian

 

[AlphaMethylPhenyl]

Chronic oxycodone induces axonal degeneration in rat brain


Opioids aren't so physically healthy on their own. We're going to see a windfall of these kind of studies in not too long. The government no longer sanctions huge doses of opioids over long periods of time, or at least is getting there.

We're talking

1. Apparently maladaptive apoptosis
2. Demyelination, leading to apoptosis/necrosis more likely

From: an increased stress response.

 

[Dresden]

PROFESSOR CHRISTINE WHITLOCK

 

[clubcard]

Since it's identical to cocaine subjectively, I think C++ deals with it. The more observant will realize that a p-NO2 is dubious. Tried all manner of other moieties so I can only presume lone-pair interactions coupled to steric bulk are involved so it might help map out certain ligands. I certainly wouldn't be rushing out to take the stuff since I hate cocaine for numerous reasons. Didn't try methylsulfonyl (or I forgot to add it to the long list with the title 'no good'.

https://imgur.com/K5mvXRc

 

[Dresden]

Carbomethoxies are tasty; that doesn't have one. Yeah, it's still got one fruity ester, though. I'd try it with a 3,4-MDO instead of a p-NO2. Also, the bare phenyl version might be nice.

HILLARY "JANICE" CLINTON

BERN THOMPSON
[heptedrone]

Go Switzerland!!!

LANE

ALLISON

-wards off vampires
-found in garlic cloves

 

[polymath]

^ Make that react with chlorine gas and you probably have something really nasty at your hands, lol...

 

[clubcard]

Obviousiol. Do you know I actually pointed this out to the DEA and they were NOT interested so knock yourselves out. Just remember the 5HT2b affinity causes heart-valve damage.