The (±)-cis isomers [racemate (1:1-mixture) of the (4R,5S)-isomer and the enantiomeric (4S,5R)-isomer] generally synthesized from dl-phenylpropanolamine in one step by cyclization with cyanogen bromide (sometimes prepared in situ by reacting sodium cyanide with bromine).

Alternate synthesis routes generally involve more steps, such as replacing cyanogen bromide with sodium or potassium cyanate to form an intermediate and then reacting it with concentrated hydrochloric acid.

A method reported in microgram replaced the need for a separate addition of hydrochloric acid by starting with the hydrochloride salt of the dl-phenylpropanolamine but side-products are noted.

The cyanate reaction proceeds differently from the cyanogen bromide and transforms norephedrine into trans-4-methylaminorex instead, as noted in the DEA micrograph.

Moreover, 4-methylaminorex does not have the established safety profile of widely used clinical psychostimulants such as methylphenidate and dextroamphetamine.

First study[10] using quite high doses (highest dose caused clonic seizures and some rats died) in rats and studying short-term effects (rats were killed 30 min to 18 h after injection of 5, 10 or 20 mg/kg of racemic cis-4-methylaminorex) suggested reduction in tryptophan hydroxylase (TPH) activity (a possible marker for serotonin neurotoxicity) but citing study: "No change in TPH activity was observed 30 min after injection; by 8 h the activity of this enzyme appeared to be recovering."

A study[11] published 2 years later than first one also suggested reduction in tryptophan hydroxylase activity, they used quite high dose too (10 mg/kg of cis-4-methylaminorex) and studied also long-term effects (rats were killed 3 h, 18 h or 7 days after injection), they found reduction of 20-40% of tryptophan hydroxylase (TPH) activity and "recovery of TPH activity occurred 18 h after treatment, but was significantly decreased again by 7 days."

but "It is noteworthy that, unlike the other analogs, the striatal levels of 5-HT did not decline with TPH activity following multiple 4-methylaminorex treatment" The latest study[12] (using mice) was not able to find any long-term effects suggesting neurotoxicity and instead found an increase in serotonin levels, they also used high doses (15 mg/kg of each isomers studied) "The dosages used in the present experiments are about 6-10 times than the effective doses of aminorex and stereoisomers inhibition of food intake."

It was reported that although multiple doses of 4-methylaminorex caused long-term, i.e., seven-day, declines in striatal tryptophan hydroxylase activity in SD rats, no changes were found in 5-HT and 5-HIAA levels (Hanson et al.

[9] That first study [11] also suggested reduced dopamine (DA) levels (a possible marker for dopamine neurotoxicity), but citing study: "However, 8 h after drug administration no differences from control values were seen in DA, DOPAC or HVA levels."

[25][21][26] Many other monoamine releasing agents (MRAs), such as many amphetamines, are rodent and/or human TAAR1 agonists.

[21][26][25] The results of animal experiments conducted with this drug suggest that it has an abuse liability similar to cocaine and amphetamine.