Table 3. A summary of pharmacokinetic studies on aminorex and its analogs.

Aminorex
Model organism	ADME	Results	Study
In vivo: human subjects; in vitro dissolution	A	Aminorex fumarate, as sustained-release tablets in doses of 15 and 20 mg/tablet, was determined to have good absorption rates and allow for prolonged effects.	Cressman et al.211
In vivo: Standardbred gelding horses; in vitro: horse liver microsomes	M	Aminorex and rexamino were discovered to be metabolites of levamisole in horse urine and plasma.	Ho et al.63
In vivo: Thoroughbred horses	A, D, E	Aminorex was administered orally and i.v. Distribution could be described by a three-compartment (with half-lives of 0.04, 2.30 and 18.82 hours) and a two-compartment model, respectively. The substance was renally eliminated and urinary excretion peaked after two hours for the i.v. group and six hours for the p.o. group.	Soma et al.213
4-methylaminorex
In vivo: Sprague-Dawley rats	M, E	4-MAR is mostly eliminated renally (and secondly via the GIT) in its unchanged form (60%). Three metabolites could be identified: 4-MAR is hydrolysed to norephedrine, the phenyl ring can be hydroxylated to form 2-amino-5-[p-hydroxyphenyl]-4-methyl-2-oxazoline and deamination leads to metabolite 5-phenyl-4-methyl-2-oxazolidinone.	Henderson et al.216
In vivo: Wistar rats	E	4-MAR isomers could be detected by more than half of the tested on-site immunoassays, mostly as (meth-)amphetamine or cocaine. How to detect and quantify 4-MAR in urine using TLC and GC/MS is described in detail.	Kankaanpää et al.217
In vitro	A	Chemical properties of the stereoisomers are described in detail.	Klein et al.129
In vivo: Wistar rats	A, D, M, E	Oral bioavailability of 4-MAR was significantly lower than after i.v. or intraperitoneal administration. Marked differences between the isomers concerning their half-lives were found (for details see main text). Elimination of the trans-4R,5R-isomer was 3 times slower than that of the others. The highest concentrations of 4-MAR were located in the kidney, liver, brain and muscles, suggesting a significant ability to cross the blood-brain-barrier. The metabolites norephedrine (from the cis-isomers) and norpseudoephedrine (from the trans-isomers) were detected in blood and brain.	Meririnne et al.154
4,4’-dimethylaminorex
In vivo: Wistar rats	A, D, E	1 mg/kg cis-4,4′-DMAR was given i.v. The compound was more rapidly and extensively distributed than 4-MAR and more slowly eliminated (plasma t1/2 of 5.14 ± 0.65 h). I.p. doses of cis-4,4′-DMAR (1, 3 and 10 mg/kg) show a dose-dependent AUC. Data was quantified with HPLC-MS/MS.	Lucchetti et al.214
In vivo: Wistar rats	A, D, M	I.p. injections lead to fast brain absorption (tmax = 30-60 minutes) and high brain concentrations with a brain-to-plasma ratio of 24. The t1/2 was determined to be approximately 50 minutes. Four metabolites, caused by hydroxylation, oxidation, hydrolysis and oxidative deamination of cis-4,4′-DMAR were identified in plasma and in low concentrations also in the brain. Behavioural experiments highlight the rewarding and addictive properties of cis-4,4′-DMAR.	Lucchetti et al.215