Ketamine salts solubility

[FormerBeagle]

I guess the other question is whether the carbamate would cleave in an appreciable amount to release an active dose, or if it would be active on it's own.

Yeah that is definitely one of the interesting topics at hand. The carbamate of placidyl for example is more potent than the parent, and the same holds true for simple alcohols (e.g. ethanol vs ethyl carbamate). But it is unclear to me if this is a pharmacokinetic effect (sneaking the drug past first-pass metabolism), or if the carbamates are active themselves.

here is conflicting ish data on whether propofol binds the transmembrane helices as solvent anesthetics or closer to the pores as barbiturates do. If it binds at the transmembrane helices it may be less amenable to adding bulk than the barb region.

Interesting. I've not really studied this aspect closely, but I think that barbiturates are allosteric modulators of GABA-A receptor, but I think that the volatile anesthetics do not need GABA to act. Not sure about propofol. I thought that the binding sites of propofol and barbiturates and benzodiazepines were all separate. I'm tempted to suspect that the binding site for propofol would be overlapping with an endogenous neurosteroid like the recently approved brexanolone (allopregnanolone).

nother thing to look into would be the kinetics of fospropofol, could be enlightening.

Pretty sure that fospropofol is propofol by the time it gets to the CNS.

 

[Skorpio]

I was incorrect in my comment about propofol binding sites. It binds to both the barb and etomidate sites on GABA A. Linked is a paper that sums it up nicely.

Identifying drugs that bind selectively to intersubunit general anesthetic sites in the α1β3γ2 GABAAR transmembrane domain

GABAA receptors (GABAARs) are targets for important classes of clinical agents (e.g. anxiolytics, anticonvulsants and general anesthetics) that act as positive allosteric modulators (PAMs). Previously, using photoreactive analogs of etomidate ([3H]azietomidate) and mephobarbital...

molpharm.aspetjournals.org

 

[sekio]

most carbamates are resistant to metabolic degradation, e.g. methocarbamol is not "decarbamated" to guaifensin in vivo.

 

[FormerBeagle]

Interesting. I just assumed that they would be cleaved by esterase. Ethyl carbamate is hydrolyzed at the carbamate group at least to some extent. But looks like for the carbamates in methocarbamol and carisoprodol (and meprobamate) this is not a primary pathway. I really proposed this compound as a conversation starter more than anything. And didn't really think that I had any phosgene laying around anyway. Did just notice some triphosgene though. So perhaps if I get bored enough...

 

[polymath]

Last weekend, I extracted melatonin from about a 100 tablets with 1.9 milligrams melatonin per tablet. Soaked the tablets in about 1 dl of technical grade ethanol, and after a while filtered the solids with a cotton filter (the fillers in the tablets are mostly crystalline cellulose which doesn't dissolve in water or ethanol). Then added a bit of solid potassium hydroxide in the ethanol solution and kept it in a closed bottle at room temperature for over 16 hours. After that, I added about 2 dl of saturated sodium chloride solution to make the mixture polar, and then extracted with de-aromatized mineral spirits. Finally, I shaked the non-polar phase with vinegar (10% acetic acid) and separated the phases in a separatory funnel.

After evaporating the water and acetic acid, a bitter-tasting residue was left, and it probably contained some mexamine (5-methoxytryptamine) due to alkaline hydrolysis of the melatonin. Melatonin itself doesn't taste bitter like most alkaloids do. The only other possible explanation is that the taste was due to some denaturant in the tech. ethanol that somehow ended up in the final product. There was some NaCl and potassium acetate as an impurity in the residue, because some emulsified droplets of aqueous phase remained in the mineral spirits layer after separating the phases. Therefore, the final product was too impure to smoke (tried to do that, mixed with oregano and rolled into a cigarette, but the salt impurity acted as a fire retardant making that impossible).

Anyone ever tried whether mexamine has any effect when smoked? Shulgin reports that tryptamine itself is active at parenteral doses of 200+ mg. If the 5-methoxytryptamine is about 10-25 times more potent (as is the case when comparing other tryptamines to their 5-methoxylated counterparts), then it could be possible to inhale enough in a couple of puffs.

Note that this could be illegal in USA (unlike here), due to the controlled substance analogue act.

 

[polymath]

^ I remember thinking about open chain versions of methylphenidate many years ago... Difficult to guess whether alpha-methyl (as in the image above) or alpha-ethyl is more effective in that case.

 

[negrogesic]

"PHREEX ('Dave')
N-methyl-3-oxo-hexahydromorphinan
Should be a potent opiate."

Pretty slick

 

[Dresden]

Thx!

ELLIE

 

[Gaffy]

NELLIE

KNEELLIE

 

[phenethylo J]

Eos

Her rays of light dispersed the mists of night.

 

[S.J.B.]

Discovery of conolidine derivative DS39201083 as a potent novel analgesic without mu opioid agonist activity
Corresponding author: Tsuyoshi Arita (R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan)
Bioorganic & Medicinal Chemistry Letters 2019, Volume 29, Issue 15, Pages 1938-1942
Published online May 21st, 2019
https://doi.org/10.1016/j.bmcl.2019.05.045

We discovered a novel compound, 5-methyl-1,4,5,7-tetrahydro-2,5-ethanoazocino[4,3-b]indol-6(3H)-one sulfuric acid salt (DS39201083), which was formed by derivatization of a natural product, conolidine. DS39201083 had a unique bicyclic skeleton and was a more potent analgesic than conolidine, as revealed in the acetic acid-induced writhing test and formalin test in ddY mice. The compound showed no agonist activity at the mu opioid receptor.

 

[Dresden]

Hello, CLARICE.

I Learned It All From You, Gurl.
I Got It All From You.
Oh, How To Scatch A Dog, How To Buy A BMW.
I Do It Everyday.
Come Back Again Tomorrow.

To Reiterate, These Are A Few Of My Favorite Things That I've Actually Tried So Far:

ANDREW (hmm, interesting)

EVELYN (very, very good)

DOLLY (it's Valentine's day every time you take 4-MMC!)

SID (veritas)

LUKE (super spiritual)

I also like shrooms, a-pvp, and pma, which I have also successfully sampled and didn't OD on. Your mileage may vary. I have high hopes for Stephen (N-ethyl-PMA) and Ellie [1-(3,5-dimethoxy-4-chlorophenyl)-2-aminopropane]. Shiva (3,4,5-trichloroamphetamine) wasn't bad, but there is some amount of health controversy surrounding the halogenated amphetamines at this time. Just my 10 cents. Yours truly, AMP. Fruits of the Spirit, Folks, Fruits Of The Spirit.

ADAM

EVE

STEVE

SOPORIFIC

a BEE

a WASP

an ANT

an EAGLE

a CARDINAL

a BLUE JAY

a CHILL PILL

a CHILLER PILLAR

a sedating antipsychotic (major tranquilizer)

ANGIE

IDAHO

WILEY

THE SPIRIT MOLECULE, which is all pervasive, and

JERNIGAN also make the cut, though they are qualitatively nothing alike. And let's hear it for the occasional amphetamine binge or two!

AMP
2-AMino-1-Phenylpropane
Alpha-MethylPhenylethylamine

(2S,5R,6R)-2-carbomethoxy-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-mercura-1-azabicyclo[3.2.0]heptane


FREDDIE

for when penicillin's not killin it

HEXAHYDRODEACETYLATEDDIMETHOXYLATEDBISACODYL. also know as 1,1-bis-(4-methoxyphenyl)-(2-piperidinyl)methane

 

[Gaffy]

FENDY
C1=CC=CC=C1C(C(N2CCCC2)=O)C3CCCCN3[H]

 

[sekio]

Complete biosynthesis of opioids in yeast

Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines despite diverse market demands and uncertainty in crop yields due to weather, ...

www.ncbi.nlm.nih.gov

Science. 2015 Sep 4;349(6252):1095-100. doi: 10.1126/science.aac9373. Epub 2015 Aug 13.
Complete biosynthesis of opioids in yeast.
Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD.

Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.

 

[Dresden]

MURDOC

AUNT BEATRIX DIRTY HARRY POTTER

DRUIDY DREW aka (also known as) 2D

1-phenyl-1-carbomethoxy-1-(2-pyrrolidinyl)methane
an (n -1) homologue of dexmethylphenidate

CHILLS 420

aka 7,7-dimethyl-3-pentyl-6-oxa-1,17-dihydroxy-12,13-dimethyl-6,7,8,9,14,16,17-heptahydrocyclopenta[a]phenanthrene

Possible Alien Sex Hormone.


* * *

ANDROGYNY

17-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,13,14,15,16,17-hexadecahydrocyclopenta[a]phenanthrene

* * *

POSSIBLE DESIGNER ANDROGEN
by AMP

7-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,13,14,15,16,17-hexadecahydrocyclopenta[a]phenanthrene-3-one

* * *

Less Is More, More Or Less.

BELINDA
1,7-diphenyl-2,6-di-oxo-pyrrolizidine

EROS
1,7-di-(3,4-methylenedioxyphenyl)-2,6-di-oxo-pyrrolizidine

JETHRO
1-phenyl-7-(3,4-methylenedioxyphenyl)-2,6-di-oxopyrrolizidine



It's Just

TWO DOPE BOYS IN A CADILLAC.
1,4-di-(1-methyl-2-(3,4-methylenedioxyphenyl)ethyl)piperazine

TWO TWEEKERS IN PARADISE
1,4-di-(1-methyl-2-phenylethyl)piperazine

HOLLY_WOOD.
1-(2-phenyl-1-methylethyl)-4-(2-(3,4-methylenedioxyphenyl)-1-methylethyl)piperazine

FAR OUT
2,6-di-oxo-N-(2-(indol-3-yl)ethyl)pyrrolizidinium

Yeh, man.

EVEN FURTHER
2,6-di-oxo-N-(2-(5-methoxyindol-3-yl)ethyl)pyrrolizidinium

LE HARLEQUIN
2,6-di-oxo-N-(2-(4-hydroxyindol-3-yl)ethyl)pyrrolizidinium

ICP (which stands for either Inductively Coupled Plasma or Insane Clown Posse, your choice)
2,6-di-oxo-N-(1-propyl-2-(3,4-methylenedioxyphenyl)-2-oxoethyl)pyrrolizidinium



A Large Portion Of This Post Has Been Made Possible By The

PYRROLIZIDINE

Molecule. Thanks For Reading!

AMP
2-amino-1-phenylpropane or

ANDREW
phenyl piperidin-4-yl ether

Hmm...Interesting!

MARK
2,6-di-oxo-1,7-di-phenoxypyrrolizidine

¡C'est Arte!

JOHN
3,5-dimethyl-1,7-dioxo-2,6-diphenylpyrrolizidine

PETER

TIMOTHY
3,5-dimethyl-1,7-dioxo-2,6-di-(3,4,5-trimethoxyphenyl)pyrrolizidine

MARY
2,6-dioxo-1,7-di-(3,4-methylenedioxyphenoxy)pyrrolizidine

Follow Where Mary Goes
Cherish The Things She Knows
Said When I Change My Stride,
Then I'll Fly.

LUKE
2-ethylamino-2-(3-methoxyphenyl)-cyclohexanone

PHILLIP
1-cyclohexyl-2-aminopropane

LEE
super potent dopamine reuptake inhibitor

CRONOS [FATHER TIME]
4-methoxyindan-6-yl piperidin-4-yl ether

Time, Time, Ticking, Ticking Away...

DANIEL
1-(4,7-dimethoxyindan-6-yl)-2-aminopropane

AMPED UP
1-(2,5-dimethoxy-3,4-dichlorophenyl)-2-aminopropane

EZEKIEL
1-(2,3-dichlorophenyl)-1-methylaminocyclohexane

ROSIE
1-(2,3-methylenedioxyphenyl)-1-ethylaminocyclohexane

Riveting!!!

DESIGNER ESTROGEN
2,3-methylenedioxy-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene

OPIOID x THC HYBRID
N-ethyl-1-hydroxy-3-pentyl-6-oxomorphinan

some kind of
CRAZY FEMALE AMP OPI MDO STEROID HORMONE!
12-oxo-7-(2-phenyl-1-methyl-ethyl)amino-2,3-methylenedioxy-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene

HIMS, this one's for the guys; should be fun.
12-oxo-7-(2-phenyl-2-carbomethoxy-1-methyl-ethyl)amino-17-acetoxy-13-methyl-1,2,3,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3-one

THE BRASS MONKEY
1,4-di-(1-methyl-2-carbomethoxy-2-phenylethyl)-piperazine

THE FLYING MONKEYS
1,4-di-(1-methyl-2-carbomethoxy-2-(3,4,5-trimethoxyphenyl)ethyl)-piperazine

THE PSYCHIC MONKEYS
1,4-di-(1-methyl-2-carbomethoxy-2-(3,4-methylenedioxy-5-methoxyphenyl)ethyl)-piperazine

THE DEAD MONKEYS
1,4-di-(2-(4-methoxyphenyl)-1-methylethyl)piperazine

THE GAY MONKEYS
1-(1,3-benzodioxol-5-yl)-2-methylaminopropane

THE SEX CRAZED MONKEYS
1-(3,4-methylenedioxyphenyl)-1-oxo-2-(1-pyrrolidinyl)-pentane

GYRO
1-(3,4-methylenedioxyphenyl)-1-oxo-2-(1-piperidinyl)-propane

BIG BARE PHENYL
(Ursa Major).
1-phenyl-1-oxo-2-(1-piperidinyl)-propane

REBA
1-phenyl-1-oxo-2-(4-morpholinyl)-propane

SUPER FUN
1-phenyl-1,1-di-carbomethoxy-1-(2-pyrrolidinyl)-methane

SIRIUSLY
4-Methyl-Indol-3-yl N-methyl-piperidin-4-yl ether

The End.

 

[polymath]

^ Those genes could be inserted in the gut microbes of someone who has a huge opioid tolerance, as an alternative to methadone maintenance... Well, maybe not...

 

[polymath]

The alkaloid glaucine, found in some poppy plants, is a real 5-HT2A agonist...

In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors - PubMed

Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT₂ and α₁ adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in...

www.ncbi.nlm.nih.gov

Abstract
Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb = 8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.

 

[S.J.B.]

The alkaloid glaucine, found in some poppy plants, is a real 5-HT2A agonist...

Apparently it's been sold as a "legal high" in the U.K.

 

[polymath]

^ There are some trip reports about it on Erowid and other places. Most people seem to say it makes you feel really tired, like an alpha-2-adrenergic agonist. I'd like to see a halogen or methyl substituent added to one of those aromatic rings, maybe it would increase the psychedelic component of the effect.




Edit: BTW, I also added (anonymously) the reference above to the Wikipedia article about glaucine.

 

[Dresden]

DOPAMINE, (DA).
1-(3,4-dihydroxyphenyl)-2-aminoethane.

ADRENALINE
(1R)-N-methyl-1-(3,4-dihydroxyphenyl)-2-amino-1-hydroxyethane

NOREPINEPHRINE, (NE).
(1R)-1-(3,4-dihydroxyphenyl)-2-amino-1-hydroxyethane

SEROTONIN, (5-HT).
5-hydroxytryptamine

N-METHYL-DOPAMINE
1-(3,4-dihydroxyphenyl)-2-methylaminoethane

N-ETHYL-DOPAMINE
1-(3,4-dihydroxyphenyl)-2-ethylaminoethane

OXO-ADRENALINE
1-(3,4-dihydroxyphenyl)-1-oxo-2-methylaminoethane

OXO-ETHYL-ADRENALINE
1-(3,4-dihydroxyphenyl)-1-oxo-2-ethylaminoethane

TRIOLAMINE
1-(3,4,5-trihydroxyphenyl)-2-aminoethane

PSI-TRIOLAMINE
1-(2,4,6-trihydroxyphenyl)-2-aminoethane

TYRAMINE [MONOLAMINE]
1-(4-hydroxyphenyl)-2-aminoethane

2,4-DA
1-(2,4-dihydroxyphenyl)-2-aminoethane

3-MONOLAMINE
1-(3-hydroxyphenyl)-2-aminoethane

4-HYDROXY-TRYPTAMINE, (4-HT).
1-(4-hydroxyindol-3-yl)-2-aminoethane

PEA
1-phenyl-2-aminoethane

TRYPTAMINE, (T).
1-(indol-3-yl)-2-aminoethane

2,6-DA
1-(2,6-di-hydroxyphenyl)-2-aminoethane

These Are Just A Relatively Small Portion Of The Possible Neurotransmitters In The Universe. Our Brains Only Use About 3 Or 4 Of Them, But Through Chemistry, These And Many More ' NEW WAYS OF THINKING' Can Be Explored.

BLUE HYACINTH
1-(2-phenyl-1-methylethyl)-4-(3,4-methylenedioxyphenyl)-piperazine

WILD HONEYSUCKLE
1-(2-(3,4-methylenedioxyphenyl)-1-methylethyl)-4-(2-methoxyphenyl)-piperidine

BzP, where P = piperazine, a mild stimulant, not to be confused with...

BzP, where P = piperidine, another mild stimulant.

CRUNK JUICE
1-benzyl-4-(2-phenyl-1-methylethyl)-piperazine

CRUNKY BREWSTER
N-benzyl-2-carbomethoxy-4-(2-phenyl-1-methyl-2-carbomethoxyethyl)-piperazine

METHYL JASMONATE, my favorite scent.

PINNACLE, a possible antiretroviral agent.

HOWARD
1-(2,6-dimethoxy-4-iodophenyl)-2-(2-oxopyrrolidin-1-yl)-ethane.

HUGHES
1-(2,6-dimethoxy-4-iodophenyl)-2-(pyrrolidin-1-yl)-ethane-1-one.

2C-aPVP:
STIMULATORY STUD OR DUD?

Let Me Know In Time.
Let Me Know In Time!

STEPHEN or STEPHANIE
1-(4-methoxyphenyl)-2-ethylaminopropane

PATRICK aka PCP or 'Angel Dust.'
1-phenyl-1-(1-piperidinyl)-cyclohexane

MORRISSEY
1-phenyl-2-(1-pyrrolidinyl)-propane.

STACY
1-(3,4-methylenedioxyphenyl)-2-(1-pyrrolidinyl)-propane

ANDREA
1-phenyl-1-oxo-2-(1-pyrrolidinyl)-propane

ASHLEY
1-(3,4-methylenedioxyphenyl)-1-oxo-2-(1-pyrrolidinyl)-propane.

ANNA, usually chewed out of the leaves or else chemically extracted from them of the fresh African khat plant cuttings; better known as cathinone.
1-phenyl-1-oxo-2-aminopropane

Nice Women, Nice Women, Nice Women.

JOY!
1-(3,4-methylenedioxy-5-methoxyphenyl)-1-phenyl-2-aminopropane

* * *

HALLELUJAH!!!
HALLELUJAH!!!

T-T-T-TOKE-E-O!!!!
1,1-di-(indol-3-yl)-2-dimethylaminoethane

The Pen Is Mightier Than The Sword.

KING PENTHEUS
1,1-di-(4-chloroindol-3-yl)-2-aminopropane

Have You Seen The Light?

ANGELINA JOLIE
-2,6-di-oxo-1,7-di-(3,4-diacetoxyphenyloxy)-pyrrolizidine
-heroin like opioid and then some

BRAD PITT &
-1,1,1-tri-(indol-3-yl)-2-dimethylamino-ethane
-Dreamy.

THE PENDULUM
-1,1-di-(3,4-methylenedioxy-5-methoxyphenyl)-2-aminopropane
-Period of Pendulum, T = 2pi times (length/g)^(1/2).

TRYPTAMINE TRAIL MIX
1-(indol-3-yl)-1-(4-hydroxyindol-3-yl)-1-(5-methoxyindol-3-yl)-2-dimethylaminoethane

JWH-073
-1-(1-butylindol-3-yl)-1-(naphthalene-1-yl)methanone
-somewhat safe and manageable synthetic 1-alkylated 3-carbonyl indole cannabitomimetic

JWH-0091
-1,1-di-(1-pentyl-4-methylindol-3-yl)-methanone

H-(C=O)-H
-methanone
-formaldehyde
-sherm
-embalming fluid
-wet

CH2CH2OH
-ethanol or ethyl alcohol
-the kind people drink

The End.