German Translation Help

[paracelsius]

Need help translating this German abstract:

Diese Verbindung besitzt am Tetrahydro-1,4-oxazinring keine Methylgruppe. Ihre Toxicität beträgt bei subcutaner Injektion bei weißen Mäusen 350 mg/kg, bei peroraler Verabfolgung bei weißen Mäusen liegt die LD50 bei 730 mg/kg. Auch diese Verbindung wirkt bei Ratten und Mäusen stark zentralerregend, ist bei Hunden jedoch wirkungslos. Orientierende Versuche am Menschen haben ergeben, daß dieser Körper auch hier keine zentrale Erregung, sondern eher eine Sedation hervorruft. Auch diese Substanz zeigt am Blutdruck deutliche Tachyphylaxie. Die pressorische Wirkung ist etwa 500--1000mal schwächer a|s die des Adrenalins.

I don't get it. Are they saying the compound is a potent central stimulant ("Stark zentralerregend") but next sentence they talking about sedation: ("sondern eher eine Sedation hervorruf"). Is it a stimulant or a sedative? may be depending on dose or what? can't be both at same dose.. they haven't given any dosage info tho. Kind of confusing. Only LD50 in mice but no dose for central stimulation and/or sedation activity. Thanks a lot for your help. Y'all have G'day.

 

[Fertile]

'This compound has no methyl group on the tetrahydro-1,4-oxazine ring. Its toxicity when injected subcutaneously in white mice is 350 mg/kg, when administered perorally in white mice the LD50 is 730 mg/kg. This compound also has a strong central stimulating effect in rats and mice, but is ineffective in dogs. Preliminary experiments on humans have shown that this body does not cause any central excitation, but rather sedation. This substance also shows clear tachyphylaxis on blood pressure. The pressor effect is about 500-1000 times weaker than that of adrenaline.'

So it's a stimulant in some animals, sedating for humans. 'tachyphylaxis on blood pressure' isn't exactly the correct translation, I don't think, but it is a bit technical.

I cheated, I ran it through 4 different translation pages and used my VERY basic German just to guesstimate which was most appropriate. But it does answer your question, I hope.

 

[TheUltimateFixx]

Native speaker here, the above poster has it correct. It causes marked stimulation of the central nervous system in rats and mice, has no effect of any kind on dogs, and is sedating in humans.

 

[paracelsius]

Thanks a lot guys. Now it is even more interesting than I first thought. So they tested it in humans too? Missed that one. Thought they’re only talking about rat (“ratten”) and mouse (“mausen”) "stimulant" and "sedative" at same time. Now that makes sense!

So it is stimulant in mice and rats and sedative in humans. Quite unexpected. Because you see, actually this compound is the simple 2-phenyl morpholine, that is phenmetrazine without the 4-methyl (tetrahydro-1,4-oxazine is old (formal) name for morpholine). So one would expect it to have central stimulant effect like phenmetrazine but sedative?

Because if you look at the (recent) patent for 3-FPM and other phenylmorpholines, it is (PAL-632 there) actually as potent as Phenmetrazine as a DA-NE releaser (doesnt have any serotonergic): EC50 DA-NE-SERT 86, 79 and 20,200nM resp. Phenmetrazine is 130, 50 and 7,765 nM. So I would expect it to have stimulant properties like Phenmetrazine. But apparently it is sedative in humans.

I think it is probably sedative at low dose and stimulant at higher doses, similar to fencamfamine-type stimulants. Sedative at 25mg or less and strong stimulant above. I wish that German paper gave the dose they used in humans tests. But anyhow, looks preffy safe LD50~750mg/kg po (+amph is like 125mg/kg in mice po?? I will definetely try that compound. It is dirt cheap and available all over with fine chem houses. Or may be I’ll even make it myself have some phenylethanolamine laying around. 3-FPM was nice, very functional below 100mg.

 

[paracelsius]

I’ve seen bunch of ring substituted phenylmorpholines (3-CPM, 4-Me-PM..etc) popping up lately before 3-FPM got worlwide UN ban soon. But these are all with a 3-methyl on the morpholine. Now if Aminorex type oxazolines (4-MAR...etc) effect is any indication, unsubstituted morpholines (unsubstituted on the morpholine that is) would be really really good. I mean plain Aminorex was as euphoric as 4-MAR. More like meth (w/w) I would say but lasts forever...well just like meth which I hated the super long duration. So if anything that compound would be more like plain Aminorex.

Now I wonder how that compound acts like a sedative. I mean the mechamism. Never heard about Phenmetrazine or analogs having sedative activity. I guess the provervial "magic methyl" medicinal chemists like to call it! Could it have some GABAergic like phenybut, baclofen..etc by removing the methyl?? The structure looks like a cyclized distant relative of these. I am not famliar with SAR of these compounds, but could it be the sedation is due to that. Anyhow will try that one soon. Thanks again guys and you have G'day....