Unusual / uncommon alkaloid drug salts

[resorcinol]

... you've seen?

I've seen a few ones that are quite uncommon. The common salts of alkaloid (amine group containing) drugs are these salts (X will represent the alkaloid drug): X hydrochloride, X sulfate, and X citrate. These three (especially HCl salts) seem to dominate. There are rare exceptions where certain drugs are almost never marketed as these salts though.

Some examples (the + and - are charges, and ~~ means an ionic bond when in solid form ... the symbols part are structural formulas of the chemicals that show where the ionic bond is and how many cations and anions are in each molecule of the substance):

*dextromethorphan hydrobromide (cation:anion ratio is 1:1) {recreational dissociative, cough suppressant}

[DXM-H]+ ~~ Br-

*escitalopram oxalate (cation:anion ratio is 1:1) {SSRI; Lexapro}

[escitalopram-2H]2+ ~~ [oxalate]2-

*imatinib mesylate (cation:anion ratio is 1:7) {drug for CML, leukemia, highly effective drug}

[imatinib-7H]7+ ~~ [7[mesylate]]7-

*codeine phosphate (cation:anion ratio is 3:1) {mild opioid mu agonist, fun as hell w/ no tolerance, great for w/d even w/ tolerance}

[3[codeine-H]]3+ ~~ [phosphate]3-

*doxylamine succinate (cation:anion ratio is 1:1) {extremely sedating H1 antagonist [antihistamine]}

[doxylamine-2H]2+ ~~ [succinate]2-


*******removed tl;dr part that was right smack in the middle here. it was SO long that the board wouldn't let me post it due to it being too long for a post. Wow. I've gotta chill with the length of some of these posts! **************



Anyway, got way way way fucking OT. I thought of another uncommon salt for a common drug...

*clemastine fumarate {very potent antihistamine on a mg basis; 1 mg = 50 mg diphenhydramine aka benadryl as an antagonist of H1 receptors ... brand name is Tavist and it's OTC in the U.S.}

[2[clemastine-H]]2+ ~~ [fumarate]2-


It's not often AT ALL that you see fumaric acid used to salt a pharmaceutical drug that's a base. Actually clemastine is the only one I've ever seen as a fumarate. Clemastine fumarate is the antihistamine Tavist btw (lots of people probably have never heard of it, it's not the most well known antihistamine at all). It's very potent. I find the most effective sedating antihistamine to be dexbrompheniramine (but it only comes combined with other crap in drixoral ... or racemic combined with other crap in dimetapp ... I'd love to see it marketed standalone ... it's much more effective than its chlorine analog chlorpheniramine IME) and the most effective non-sedating one to be fexofenadine (which is not potent at all by mg strength but is very powerful). I think that Tavist (clemastine fumarate) is the most potent antihistamine (strongest, highest affinity for H1 receptors as an antagonist) I've ever seen though, Rx and non Rx both included. 1 mg clemastine freebase (1.34 mg clemastine fumarate) = 50 mg diphenhydramine HCl ... these are the equipotent doses as antagonists of H1 receptors. Yeah, clemastine is the fentanyl of antihistamines. Potent shit right there.

Another new one I just remembered...


*Propylhexedrine phenobarbitalate (both the cation and anion are active drugs [very unique indeed] ... PHX is the base used to deprotonate the phenobarb and phenobarb is the acid used to protonate the PHX ... it's called Barbexaclone for the brand name and is used for epilepsy in Italy and a few other european countries ... some other drugs get their "own name" and are really two actives, but most aren't true salts ... like the mixture of diphenhydramine and 8-chlorotheophylline [which is a more potent analog of caffeine] sold as "dimenhydrinate" / Dramamine original version; the two are just mixed together and are not a salt so IDK why they got a new name dimenhydrinate??? Strange .... but Barbexaclone is a true salt of two drugs, one organic base, one organic acid) {recreational stimulant and barbiturate downer in one single compound held together by an ionic bond ... the stim and downer will revert to the separate, freebase and free acid forms in vivo ... used for epilepsy in Italy most often but also several other countries in the Mediterranean region ... well liked by patients, s/e of phenobarb abolished by the PHX which is a psychostimulant that acts on monoamine transporters in the same way as amphetamine}

[propylhexedrine-H]+ ~~ [phenobarbitalate]-



Phenobarb is a monoacid (can loose one acidic H atom) due to keto-enol tautomerism. The double bond in the carbonyl group that isn't adjacent to the nitrogen atoms in the ring does keto-enol tautomers. The double bond can change to being in the ring between the bond to the oxygen that is tautomerizing and the bond to the ethyl side chain off the ring. This leaves a C-single bond-O that has a neg charge. Since it has no proton to give up itself, the solution must be made acidic with a little HCl to protonate the propylhexedrine. Upon evaporation, either fractional crystallization or more advanced techniques are used to separate the propylhexedrine HCl formed from the propylhexedrine phenobarbitalate formed (both will form .. think about the ion species in the aq solution). The purified propylhexedrine phenobarbitalate is then marketed as Barbexaclone.

It's equal in efficacy to plain phenobarb when a dose with an equivalent amount of phenobarb is taken, but is far less sedating because propylhexedrine is a powerful CNS stimulant with a mech of action identical to amphetamine. So it's actually not true that there are no remaining oral uses of PHX that are totally legit after Eventin (dexpropylhexedrine HCl) 25 mg pills for weight loss stopped being manufactured -- barbexaclone is still prescribed widely for epilepsy in Italy. From what little bit I read online, it's the best rated epilepsy med in italy by patients because it lacks the s/e of phenobarb, thanks to the countering of the heavy sedation by the powerful CNS stimulant effects of propylhexedrine. In vivo the salt reverts into the freebase and freeacid of both drugs btw, its just that administering it as a salt of both drugs like that improves absorbtion and simplifies dosing since for a given dose of phenobarb a fixed amount of PHX comes along (it's always the same amount since it's a stoichiometrically fixed salt). I'm left wondering why Barbexaclone isn't an option for epilepsy sufferers in the U.S. Heck, I'm still wondering why Eventin isn't still on the market. I'm also wondering why (while otherwise awesome) Barbexaclone's mfrs didn't use dexpropylhexedrine only and used racemic. L-PHX is NASTY on the body. Granted, the doses in Bclone are low compared to PHX rec use from benzedrex, but d-PHX would still be easier on the body. I still think Eventin (d-PHX HCl) 25 mg tablets was probably lovely to get high on.

Have you guys seen any strange salts of pharma drugs that I missed? Let me know. This shit is interesting to me.

[euphoricontin17]

Hey, I don't know how uncommon this one is but- Bitartrate (sp?) as in hydrocodone bitartrate. I've never seen any other drugs with this salt.

[StackBundles]

Meconate? I don't know if meconate is a form of salt though??

[More Feen]

Yeah,

+Meconate is the salt formed with meconic acid--the predominate acid in the opium poppy.

So many of the alkaloids in opium are in the form of ______ meconate (morphine meconate, codeine meconate, etc...).

There was a veterinary book online that talks of Morphine meconate being a very suitable form of analgesic for injection in horses.

This is likely the form that is in poppy tea. The water soluable salt of morphine elutes from the ground-up pods into the liquid.

Many people want to know about ways to isolate morphine from their pods (there are several threads & posts just here at opi-file). Mostly people who experiment with different techs aren't too successful.

I think that possibly instead of focusing on isolating morphine base, people should look into isolated the morphine in its natural salted state of M-meconate. According to that one Vet source, it is suitable for needle use.

M F

[resorcinol]

Morphine is actually a zwitterion (can form a salt with an acid or a base) because it can accept a proton at its amine group or loose a proton (hydrogen positive ion) from its aromatic ring destabilized -OH (the one at position 3). The latter (morphine loosing a hydrogen / acting as an acid) is less favored and requires stronger basic conditions (pH 12 with KOH would likely form potassium morphinate) than the strength of acid conditions needed to form a salt with a base (any pH below 5 [and 7 is neutral] will form tons of the salt of morphine with the acid used) ... a mildly acidic citric acid soln will form tons of morphine citrate by protonating morphine's amine group. Morphine is a "freebase-freeacid" at pH 9.1; the fact that it's neither lost a proton nor accepted a proton (is free, plain morphine) at a pH that's BASIC shows that morphine is a stronger base / acts as a base (proton acceptor) more easily and is a very weak acid / acts as an acid only under extreme pressure to do so by strongly basic conditions. This is clear because free morphine creates a solution in water with a mildly basic pH of 9.1 ... so it's stealing some protons from the water's hydronium ions but not giving any up to increase the number of hydronium ions in the water (hence the solution of free morphine having a basic pH [which implies a deficit of free hydronium ions]). This is why morphine is often simply considered a base as when dissolved in its free true form it acts as a base (makes the water's pH alkaline by protons shifting from hydronium ions and into a coordinate covalent bond with the free e- pair on the amine's nitrogen atom in morphine) ... it doesn't do the opposite and loose any hydrogen as H+ from the 3-OH group under normal conditions ... it will only do this in an aqueous solution that is VERY alkaline (pH 12 - 13) and so short on hydronium ions that equilibrium will begin to dictate the loss of hydrogen as H+ from the 3-OH to the water where the H+ released will bind water to form some hydronium ions to try to drag the pH down towards neutral. The rxn of morphine acting like an acid at its 3-OH group thus only occurs as we can see when coerced by very alkaline conditions while the rxn of morphine binding a proton that it grabs from hydronium ions in an initially neutral sample of water which raises the pH occurs spontaneously when free morphine is added to said water; that amine group on morphine is a moderately strong base and grabs H+ to form a coordinate covalent bond with (leaving morphine with a 1+ charge and the need for an anion to balance that if one wants a solid ... a "salt" of morphine).

I mention this simply because many morphine extractions from pod material require forcing morphine to give up a proton (act as an acid) to form, usually calcium morphinate by using calcium hydroxide to increase the pH to 12, during a step of the extraction process.

Morphine is LEAST soluble in water as FREE morphine ... so, at pH 9.1 ... it's at pH 9.1 that the most morphine will ppt out of solution as freebase-freeacid (just "free" if you will ... or "freebase" is fine since morphine is a much stronger base than it is as an acid) morphine. Even free morphine is somewhat soluble in water though, so the solution of morphine must be CONCENTRATED (as much as possible) so as little M is lost as possible. You'll STILL loose a little M no matter what, but from a conc solution you'll get pretty pure free morphine precipitate provided the whole extraction was done carefully with good potent starting material.

Usually the rxn with acetic anhydride to produce heroin is carried out with free morphine (the result of the ppt of morphine that occurs at pH 9.1) ... actually maybe not usually, maybe ALWAYS ... i think in practice FREE morphine is always used as the starter for the AA rxn. The result is heroin and unreacted AA when the rxn is done. At that point, what one does is quench the unreacted AA and heroin with water. The unreacted AA will instantly hydrate to form an aqueous solution of acetic acid, and the acetic acid will protonate the heroin at the amine group to yield heroin acetate in solution and some acetic acid that didn't react w/ the heroin. Evap would drive off the acetic acid with the water, leaving heroin acetate.

At this point a person synthing H for personal use in a home H lab could really simply stop and just use the heroin acetate for snorting, injecting (IV, IM, or SC), oral (that's uncommon though, nobody uses H orally), or plugging. Heroin acetate is just as suitable for any of the routes that heroin hydrochloride is suitable for. The only good reason to rebasify to get free H, then reacidify to get heroin HCl, would be for selling b/c customers are used to getting the hydrochloride and the acetate salt will be a bit weaker by weight. Sure, you'd thus have MORE total mass of the acetate, but try explaining chemistry of salts to the avg street user ... err, not gonna work well. For personal use though, the acetate is perfect, you just use slightly more heroin acetate by mass then you'd use of heroin HCl to get the same dose (you'll have more total mass of heroin acetate then the same amt converted to heroin HCl since the amt of heroin is the same, it's the acetate making the compound less % H by mass, but there's the same total mass of H, so you'll just have MORE of the acetate salt ... make sense?). If somebody does this, just use the heroin acetate that results from quenching the finished AA + M --> H rxn with water and evaporating the water / acetic acid (which forms from the unreacted AA being hydrated; some of the acetic acid will not react with H and will be left behind but will evap with the water) solution to leave behind heroin acetate. Why add more steps when the H acetate is perfectly good for shooting, snorting, plugging ... for all the ways to use heroin? The only exception is chasing; heroin acetate can't be chased (but neither can heroin HCl). For chasing you need free heroin (not protonated to form any salt; the freebase form) OR an additive compound that has a lower vap point than either heroin acetate / heroin HCl and a lower vap point then itself when it's thoroughly mixed with the heroin acetate or heroin HCl. I know caffeine SUPPOSEDLY works as an additive for vaporizing for heroin hydrochloride ... IDK about heroin acetate and caffeine.

Back OT -- bitartrate is an uncommon salt for a drug. I actually don't know why they just didn't decide to use hydrocodone tartrate in Vicodin and the like. The bitartrate salt only partially neutralizes tartaric acid (one of the two acidic hydrogens of tartaric acid protonates hydrocodone) such that [hydrocodone-H]1+ cation and [bitartrate]1- anion are in a perfect 1 to 1 ratio ... one hydrocodone cation with one bitartrate anion in each molecule of hydrocodone bitartrate. If they'd just fully neutralized tartaric acid to form hydrocodone tartrate it'd be [2[hydrocodone-H]]2+ [tartrate]2- .... that's two hydrocodone cations with one proton added to each giving each a 1+ charge, thus giving two of them a 2+ charge, and a tartrate anion that lost two H+ giving the single tartrate anion a 2- charge. So one molecule of hydrocodone tartrate would be two hydrocodone cations to one tartrate anion, a 2:1 ratio.

It's easy to see that hydrocodone tartrate will end up having more % hydrocodone by mass than hydrocodone bitartrate does. The former is the better salt for potency, but the latter is the one used in all the hydrocodone pharmaceuticals. It's quite odd.

[More Feen]

Resorcinol,

That is a very informative post--thanks!

My good buddy has always taken the additional steps of adding water to the recently reacted AA + M-base, and then adding a heated solution of Na-carbonate & water, dropwise, until the solution stops fizzing, and turns cloudy. Left to sit for an hour, the cloudiness ppts to beautiful crystals at the bottom of the test tube. These are isolated from the supernatent, and dilute HCl is added, with saline, until the crystals go back into solution.

I'm told the resulting solution is rather pleasant.

But I might suggest to him to avoid most of those steps, maybe just make the H-acetate a little less acidic so it won't hurt the veins so much. But not so basic as to ppt anything.

M F