1-Phenyl-2-methylaminobutan-1-one

[hamhurricane]

I'm aware that there is a Buphedrone thread in BDD, but their should be a thread here as well - this chemical will no doubt see increased popularity and (ab)use in the coming weeks so i think it would be useful to consider its potential neuro/cardiotoxicity. Are their any studies which detail its pharmacology and or toxicity relative to MCAT (i was unable to find anything on pubmed) additionally has the alpha-propyl homolog (penthadrone?) been studied?

 

[Refluxer]

I don't know of any real data.

But I wouldn't think the worry is as high as with para-substituted related compounds.

 

[yaesutom]

ooh.. i'm excited to read reports when they come in - I really hope this one is more of a releaser type stimulant (like amphetamine) moreso than the crappyish feeling i get from MDPV or methylphenidate. (to me, mephedrone's stimulant effects feel more like an amphetamine... = good)

 

[seep]

...additionally has the alpha-propyl homolog (penthadrone?) been studied?

Apparently as much as 2-[cyclohexyl(3,4-dichlorophenyl)methyl]piperidine has been studied.

 

[hamhurricane]

^^^
uhhh touché?

anyway, i don't have access to medical journals ATM but which has a higher affinity for 5HT2B MA or MCAT?

 

[boohigh]

I wonder about its metablites.
As far as i know part of consumed bk-PEA are metabolised to ephedrines, that is where these bad effects on cardiovascular effects come. Remember mephedrone was said to have a toxic para-methylephhedrine metabolite. So would this apply to 1-Phenyl-2-methylaminobutan-1-one, will it have 1-Phenyl-2-methylaminobutan-1-ol metaoblite and is it more active at adrenergic receptors than ephedrine?

 

[MeDieViL]

How big is the chance of this being as neurotoxic as methcathinone?

 

[vecktor]

who knows???

to my knowledge there are currently no answers to any of these questions.

this material has been around for a while and goes back as far as the Hive, but there is still no decent data.

People are going to take shitty untested drugs in high doses no matter what and must take the consequences too.

the moron element here has been busy heavily abusing mephedrone, and they will no doubt heavily abuse this too.

 

[Twigs]

How big is the chance of this being as neurotoxic as methcathinone?

We might as well assume that it is. It should cross the BBB more easily because its less polar than MCAT, which explains the higher potency.

Here is an interesting article about MCAT's effect on the brain
http://jpet.aspetjournals.org/content/283/3/1350.full

 

[MeDieViL]

We might as well assume that it is. It should cross the BBB more easily because its less polar than MCAT, which explains the higher potency.

Here is an interesting article about MCAT's effect on the brain
http://jpet.aspetjournals.org/content/283/3/1350.full

Allright, thx!

 

[Hammilton]

Likely fair to expect 4,beta-dihydroxy metabolites. What that means, who knows. Probably nothing good.

None of the beta-keto's are going to be great drugs as far as I'm concerned. And hoping for a releaser seems like a big waste of time, since virtually all of the beta-keto and those with lengthened alpha-alkyl chains are more and more only reuptake inhibitors.

 

[seep]

Neither of the 2 you mentioned appear anywhere on pubchem or chemspider. Somebody'll add one soon.

If lengthening the alpha-alkyl component of methcathinones increases potency, is the proportionality linear or exponential?

Like consider an absurd example, heptadecaphedrone (following your naming conventions):

The cathinone version of this has a pubchem entry: 2-amino-1-phenylheptadecan-1-one

 

[hamhurricane]

LOL, it's not exponential nor liner (as im sure you know) MDPV does just fine with its alpha propyl - just a guess but butyl is probs where the potency begins to decline. i've also been thinking about the cyclic butyl analog (bk-2-benzylpiperidine)

 

[seep]

In case it's relevant, there are at least 496 bioassayed compounds with the methcathinone skeleton that have been found to be bioactive:

http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?reqid=755196912408060068&q=cids

I tried to avoid redundancies by excluding isotopes and ions.

 

[dread]

I remember reading somewhere that alpha-butyl is the peak of the potency for the lengthened alpha-alkyl chains on beta-ketones. After that, alpha-pentyl and higher, the potency should drop dramatically...

 

[De Stijl]

Likely fair to expect 4,beta-dihydroxy metabolites. What that means, who knows. Probably nothing good.

Is there a reference for 4-hydroxy metabolites of beta ketos? To my knowledge the principal metabolites are beta-OH.

A survey of the toxicities reveals no parallelism between the two methods
of determination. There is, however, a remarkable regularity of increase
in the toxicity on intravenous administration of the phenylalkanolamines
with increase in length of the side chain. Another striking fact is the much
greater toxicity of the p-tolyl derivatives (I11 and V) as compared with the
corresponding phenyl products (I1 and IV), which lends support to the
observation of de Burnaga Sanchez'O that p-methylephedrine is about 20%
more toxic than ephedrine.

AMINO-ALCOHOLS. II. HOMOLOGS AND ANALOGS OF PHENYLPROPANOLAMINE
Walter H. Hartung, James C. Munch, W. Allan Deckert, Frank Crossley
J. Am. Chem. Soc., 1930, 52 (, pp 3317–3322
DOI: 10.1021/ja01371a046

Lengthening the side chain is probably not a good idea, toxicologically speaking.

 

[boohigh]

And while the chain increase in length the peak potency increase of an effect(rush) becomes lower and lower, more like plateu.

 

[Hammilton]

Is there a reference for 4-hydroxy metabolites of beta ketos? To my knowledge the principal metabolites are beta-OH.

For para-unsubstituted phenethylamine derivatives, 4-hydroxy metabolites occur lots. With cathinones, you may be right, beta-hydroxy is probably the first metabolite, but I'd be amazed if 4-hydroxy's aren't also produced in good quantity.

 

[De Stijl]

For para-unsubstituted phenethylamine derivatives, 4-hydroxy metabolites occur lots. With cathinones, you may be right, beta-hydroxy is probably the first metabolite, but I'd be amazed if 4-hydroxy's aren't also produced in good quantity.

The ring is more stable with the ketone group in place so if oxidation of the ring is assumed to happen after reduction of the ketone wouldn't that also be seen in the metabolic pathway of pseudo/ephedrine?

The metabolism of (−)-ephedrine in man.

Summary The metabolic fate of orally administered (–)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.

European Journal of Clinical Pharmacology
Publisher Springer Berlin / Heidelberg
ISSN 0031-6970 (Print) 1432-1041 (Online)
Issue Volume 9, Numbers 2-3 / March, 1975
DOI 10.1007/BF00614017
Pages 193-198

I still think the main metabolites of concern will be the methylaminobutanols and to a lesser degree the desmethyls (the 4-carbon homologs of pseudo/ephedrine and cathine/ppa ).

 

[Rectify]

Using IUPAC nomenclature, buphedrone's chemical name should really be
2-methylamino-1-phenylbutan-1-one because m comes before p in the alphabet.