In Vitro Dissolution Rates of Aminorex Dosage Forms and Their Correlation with in vivo Availability

DARK Classics in Chemical Neuroscience: Aminorex Analogues

“…148 ■ PHARMACOKINETICS Aminorex, when available as an anorectic drug, existed in the form of 7.5−20 mg aminorex fumarate, base or pamoate tablets, to be consumed orally. 211 4-MAR seems to mostly have 189 Hereford calves an increase in arterial blood pressure but no pulmonary side-effects after daily i.v. injections (0.25 mg/kg) for one month were reported Byrne-Quinn and Grover 28 Sprague−Dawley rats dose of 1.5 μmol/kg, administered i.v., elicited increased motor activity; stereotypical behavior was not detected in doses up to 112 μmol/kg Costa et al 37 Wistar rats after administration of 6.5 to 22 mg/kg aminorex daily for 118 consecutive days, no anatomical differences in the pulmonary vessels were detectable Engelhardt and Hort 32 humans this retrospective study highlighted that anticoagulant therapy with warfarin in aminorex-caused pulmonary hypertension had beneficial effects on survival time Frank et al 190 rabbits aminorex was found to be an efficient 5-HT releaser in platelets, similar in potency to amphetamine Fristrom et al 191 human subjects two studies (79 and 60 subjects) have proven aminorex (7.5 mg) to be an effective anorectic agent, similar to dextroamphetamine and diethylpropion but more effective than phenmetrazine; side-effects concerning the CNS, the GI tract and the renal system, as well as leukopenia were reported Hadler 14 mongrel cats 1.0 mg/kg i.p.…”

“…Aminorex, when available as an anorectic drug, existed in the form of 7.5 to 20 mg aminorex fumarate, base or pamoate tablets, to be consumed orally211. 4-MAR seems to mostly have been ingested orally, insufflated or smoked in doses ranging from 5 to >25 mg depending on the routes of administration212.…”

“…Cressman and colleagues have tested the change of aminorex fumarate plasma concentration over time in human participants 211. They have shown that aminorex fumarate has a relatively long half-life of 8 hours and effects can even be prolonged and high concentrations maintained by utilizing sustained-release tablets.…”

“…The main metabolite located in plasma and brain was the one not detected in 4-MAR, caused by oxidation of 4,4'-DMAR’s para -methyl group215. It has been demonstrated that aminorex is mostly eliminated renally over the course of 72 hours211.…”

Tableting Research and Technology

“…Using an a priori assumption that a correlation exists between in vitro dissolution and in vivo availability, Cressman et al (375) evaluated changes in dosage form release characteristics in vitro before in viuo determination of total plasma radioactivity in man. Aminorex base, fumarate, and pamoate were used in solution, regular tablet, or timed-release tablet forms or, in the case of the pamoate and fumarate, in more than one dosage form.…”