trans-4-methylaminorex vs. cis-4-mar

[Bandil]

Hi!

Some time ago when the "4-mar w/o cyanogenbromide" thread was discussed it was stated that: "
It does not seem to be possible to create the less active cis-4-MAR using the cyanate route.".

This has haunted me for some time, as most(all actually) references i have read, says that the cis-isomer is the active one. Could it be that the wonder product that has been "theoretically" made is actually the less active isomer?

Edit:
According to:

http://www.erowid.org/psychoactives/law/law_fed_dea_analog_letter1.pdf

the trans isomer would actually be legal? This is great news for us european bees if it hold here aswell Thoughts?

Regards
Bandil

[Rhodium]

Stimulus properties of a new designer drug: 4-methylaminorex ("U4Euh")
Richard A. Glennon and Bryan Misenheimer
Pharmacol. Biochem. Behav. 35(3), 517-521 (1990)
DOI:

10.1016/0091-3057(90)90282-M

Abstract

Like other phenylisopropylamine derivatives, 4-methylaminorex is a central stimulant. The cis isomer of 4-methylaminorex ("U4Euh"; "ICE") has appeared on the clandestine market as a novel designer drug and was recently classified as a Schedule I substance. In the present investigation, the stimulus properties of racemic cis, racemic trans, and all four individual optical isomers of 4-methylaminorex were examined in rats trained to discriminate 1 mg/kg of S(+)amphetamine sulfate from saline. The S(+)amphetamine stimulus generalized to all of the agents investigated and the relative potencies of the optical isomers (followed by ED50 values) were as follows:trans(4S,5S) (0.25 mg/kg) > cis(4S,5R) (1.2 mg/kg) = cis(4R,5S) (1.5 mg/kg) > trans(4R, 5R). The trans(4R,5R) isomer did not completely substitute for S(+)amphetamine unless a longer (i.e., 60-min) presession injection interval was used, suggesting that it has a longer duration of onset that the other isomers of 4-methylaminorex. The results, which are consistent with established structure-activity relationships, suggest that the trans(4S,5S) isomer (which has not been scheduled) is similar in potency to (+)amphetamine (ED50=0.4 mg/kg) and is more potent than either of the cis isomers.