β-Phenylmethamphetamine (N,α-dimethyl-β-phenyl-phenethylamine)

[paracelsius]

betaphenyl-methamphetamine or seen another way a ring-opened deoxypipradol (or 2DPM) analog. Wiki doesnt say much:

β-Phenylmethamphetamine (N,α-dimethyl-β-phenyl-phenethylamine) is a potent and long lasting stimulant drug

Anybody knows how do I get hold of this paper. Pharmazie 1973; 28 (10):677. I tried like crazy; seems the journal has no online archives. unless it is a old version (would appreciate any lead ..thx

 

[dopamimetic]

Looks interesting.

I made good experiences with low dosages of desoxypipradrol (alpha-PVP too, despite it being labelled as cannibal drug and whatnot, the key lies in moderation, as always.. then you get a clean high with little physical side effects. PVP was my entry into the world of stimulants, back then I had too less of noradrenergic tolerance and would get bad side effects off amphetamine/ritalin etc..)

Unfortunately, I can't provide said paper either. "Pharmazie" sounds German, maybe I know somebody who might have access, but guess said person has no time for things like that..

 

[sekio]

"Pharmazie" sounds German,

Ding ding ding, winner. wiki: Die Pharmazie (English: The Pharmacy) is an academic journal published monthly in Berlin by Verlag Dr. W. Saenger in German only from 1946–1972, it is now published at Eschborn in English.

"Zur Pharmakologie einer Serie von Diphenylaminopropanderivaten" Schmidt D , Hüller H , Amon I , Peters R Pharmazie.1973 Oct ; 28 (10) :677-80
Abstract:
In diphenylaminopropane derivatives the substitution of the basic molecule in the amino group by aliphatic residues, benzyl or pyridyl groups leads to a reduction of the acute toxicity and to quantitative and qualitative changes of the pharmacodynamic action pattern. The compounds with the greatest analgetic activity are equal or superior to aminophenazone as regards activity. The introduction of a benzyl or pyridyl group into the molecule causes a loss of analgetic effect, but leads to an increase of the motility promoting effects. The activity of the control substance metamphetamine is reached by none of the derivatives. The anticonvulsive action of these compounds is insignificant. The effect on the blood pressure is not uniform and not very strong. As regards the spasmolytic activity, all water soluble derivatives surpass papaverine several times in vitro as well as in vivo. Pyridyl substituted derivatives attain, among other things, the double spasmolytic activity of the alkyl residue substituted DPA bodies.

Für die deutschsprachigen: den Volltext finden Sie hier. Unsuprisingly, B-phenylmethamphetamine is a locomotor stimulant (gasp), however B-phenylamphetamine is not indicated as stimulating. "None of the motility-enhancing DAP derivatives reached the activity of the comparison substance methamphetamine. [..] the most effective compounds DPA 2, 300 and 301* achieved about 1/16 to 1/2 of the morphine effect (w.r.t. hot plate test on rats) in the stated dosage. During DPA 300 and 301 their maxima of action, like morphine, was within the first 35 min [of i.p injection]. DPA 2 clearly deviated from the analgesic profile of the series with a maximum at 80 min."

DPA-1 = B-phenylamphetamine
DPA-2 = B-phenylmethamphetamine
DPA-300 = B-phenyl-N-hydroxyethyl-amphetamine
DPA-301 = B-phenyl-N-2-pyridyl-methamphetamine

 

[paracelsius]

..Unfortunately, I can't provide said paper either. "Pharmazie" sounds German, maybe I know somebody who might have access, but guess said person has no time for things like that..

thanks for trying. I don't blame you it is pretty obscure journal. I tried pretty much all databases I can think of.. but @sekio has nailed it down

@sekio: thanks for sharing the link. Nice you able to dig out that paper (what a masterstroke!.) Had a hard time getting hold of that one (buried in some old east German dusty paper archives. I bet they were looking for stims that will not show up on amphetamines piss test for sport doping!! (just a guess, I have no idea! but was common practice back then!). I bet these compounds won't show on amph piss test!

But hey.. what do you know! So beta-phenyl methamphetamine is actually an analgesic (opioid?) !! not a stim! (a least compared to meth according to the authors, my German is not as good correct me if I am wrong). Now, ½ morphine potency?? 5x demerol! that's quite amazing for such a simple compound. Then again, it looks somewhat like a N-demethylated methadone homolog without the propionyl. Methadone (and related) which are diphenylPROPYLamines

instead of diphenylETHYLamines.

I totally didn't expected it to be that potent as (opioid) analgesic (5X pethidine?!.) The SAR of methadone class opioids seems to be out of whack in this case! I bet you one of the enantiomer (the alfa-R or S not sure which one) would probably be as potent as morphine; and adding a hydroxy somewhere on one of the phenyl ring would probably jack up opioid activity by a least an order magnitude to maybe 10-20 morph. Very interesting!!

On the other hand, the parent 1,1-diphenylethylamine is a potent CNS stimulant tho in rats!! (see compound 17 here). More potent than beta-phenylamphetamine which itself is more potent than (1,1-diphenylethyl)methylamine as stim. Again, the SAR seems out of whack. May be have to do with the increased lipophilicity? Interesting tho, somehow 1,1-diphenylethylamine is metabolically pretty stable compared to phenylethylamine PEA which have a 1-2min half-life!!!.. but hey, thanks for sharing

Oh btw: the wiki entry

β-Phenylmethamphetamine(N,α-dimethyl-β-phenyl-phenethylamine) is a potent and long lasting stimulant drug.

is not quite correct: should read “beta-phenylmethamphetamine is a potent and long lasting analgesic drug with half the potency of the standard analgesic morphine in the rat hot-plate test” Not a stimulant (according to the ref the wiki entry cited!!). Guess like me, the gal/guy who posted jumped to conclusions and assume since it is a truncated version of the extremely potent NDRI stimulant desoxypipradol, it must be a stimulant!!? a bit more complicate than that I guess!!

 

[sekio]

Do note, the analgesic assay used was the mouse hot plate assay. All that it proves is the compound posesses some sort of pain-reducing effect - it's not neccesarily an opioid mechanism at work. I would bet on it being caused by norepinephrine release.

The Pharmazie paper does indicate that B-phenyl-meth is indeed a stimulant. Not as strong as meth, but stimulating nonetheless.

This actually all makes sense, amphetamine and meth are both active as analgesics in the hot plate assay.

 

[Smyth2]

thanks for trying. I don't blame you it is pretty obscure journal. I tried pretty much all databases I can think of.. but @sekio has nailed it down

@sekio: thanks for sharing the link. Nice you able to dig out that paper (what a masterstroke!.) Had a hard time getting hold of that one (buried in some old east German dusty paper archives. I bet they were looking for stims that will not show up on amphetamines piss test for sport doping!! (just a guess, I have no idea! but was common practice back then!). I bet these compounds won't show on amph piss test!

But hey.. what do you know! So beta-phenyl methamphetamine is actually an analgesic (opioid?) !! not a stim! (a least compared to meth according to the authors, my German is not as good correct me if I am wrong). Now, ½ morphine potency?? 5x demerol! that's quite amazing for such a simple compound. Then again, it looks somewhat like a N-demethylated methadone homolog without the propionyl. Methadone (and related) which are diphenylPROPYLamines

instead of diphenylETHYLamines.

I totally didn't expected it to be that potent as (opioid) analgesic (5X pethidine?!.) The SAR of methadone class opioids seems to be out of whack in this case! I bet you one of the enantiomer (the alfa-R or S not sure which one) would probably be as potent as morphine; and adding a hydroxy somewhere on one of the phenyl ring would probably jack up opioid activity by a least an order magnitude to maybe 10-20 morph. Very interesting!!

On the other hand, the parent 1,1-diphenylethylamine is a potent CNS stimulant tho in rats!! (see compound 17 here). More potent than beta-phenylamphetamine which itself is more potent than (1,1-diphenylethyl)methylamine as stim. Again, the SAR seems out of whack. May be have to do with the increased lipophilicity? Interesting tho, somehow 1,1-diphenylethylamine is metabolically pretty stable compared to phenylethylamine PEA which have a 1-2min half-life!!!.. but hey, thanks for sharing

Oh btw: the wiki entry



is not quite correct: should read “beta-phenylmethamphetamine is a potent and long lasting analgesic drug with half the potency of the standard analgesic morphine in the rat hot-plate test” Not a stimulant (according to the ref the wiki entry cited!!). Guess like me, the gal/guy who posted jumped to conclusions and assume since it is a truncated version of the extremely potent NDRI stimulant desoxypipradol, it must be a stimulant!!? a bit more complicate than that I guess!!

beta-phenylmethamphetamine can be made from Ph2CHCN the methadone precursor by Grignard addition of MeMX to the nitrile to form an acetyl group followed by reductive amination with methylamine.

A possible synthesis would be MeMgX addition to benzhydrylnitrile followed by the reduction of the intermediate imine with NaBH4 (see Diphenidine).

Starting from P2P [103-79-7], 1,1-Diphenylacetone [781-35-1] (see Diphenadione).

PhCHCN the methadone precursor is also used to make a drug called McN-4187.
Maryanoff BE, Nortey SO, Gardocki JF. Structure-activity studies on antidepressant 2,2-diarylethylamines. J Med Chem. 1984 Aug;27(8):1067-71. doi: 10.1021/jm00374a022. Erratum in: J Med Chem 1986 Dec;29(12):2534. PMID: 6747990.

α,α-DIPHENYLACETONE, Everett M. Schultz and Sally Mickey, Org. Synth. 1949, 29, 38, DOI: 10.15227/orgsyn.029.0038.