Methylenedioxyamphetamine derivatives

Large doses of the ring-substituted amphetamine derivative ( )3,4-methylenedioxyamphetamine (MDA) repeatedly administered to rats... 

Mamounas, L.A. Mullen, C. O Heam, E. and Molliver, M.E. Morphologically distinct types of serotonergic axon terminals are differentially vulnerable to neurotoxic amphetamine derivatives. Effects of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethampheta-mine (MDMA), and p-chloroamphetamine (PCA). in preparation. 

FIGURE 4 Chiral CE ESI/MS analysis of five amphetamine derivatives and two pharmaceutical compounds. Total ion current (TIC) and extracted ion currents (XIC) of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA), and tramadol (TMD) and methadone (MTD) in plasma after LLE with electrokinetic injection. 

This is the only MMDA analogue that has been explored as an N-methyl derivative. A more highly substituted analogue has also been made, the N-methyl derivative of DMMDA. Isoapiole (see its preparation under DMMDA) was oxidized with formic acid and hydrogen peroxide to the ketone (2,5-dimethoxy-3,4-methylenedioxyphenylacetone, a solid with a mp of 75-76 °C from methanol) which was reductively aminated with methylamine and amalgamated aluminum to give 2,5-dimethoxy-N-methyl-3,4-methylenedioxyamphetamine hydrobromide... 

M. A. Shaw and H. W. Peel, Thin-layer chromatography of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and other phenethylamine derivatives, J. Chromatogr., 104 201 (1975). 

F. T. Noggle, J. DeRuiter, S. T. Coher, and C.R. Clark, Synthesis, identification, and acute toxicity of some N-alkyl derivatives of 3,4-methylenedioxyamphetamine, J. Assoc. Off. Anal. Chem., 70 981 (1987). 

Amphetamine and methamphetamine possess an essentially pure psychostimulant effect however, substituted derivatives in position 3 and 4 on benzene ring are defined as entactogene [14], This class of substances includes methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), methylenedioxyethyl-amphetamine (MDEA), and others such as the /V-melhyl-l-(3-4-methylenedioxyphenyl)-2-butanamine (MBDB), methoxymethylenedioxyam-phetamine (MMDA) (Fig. 4). All of these substances are more active in the d form. There are also amphetamine-like substances which combine sympathomimetic (euphoric) and hallucinogen effects they are primary amines, trisubstituted on the benzene ring, that produce effects similar to mescaline. Among these the 2,5-dime-thoxy-4-methylamphetamine (DOM) is the most important. 

In this system, amphetamine, 3,4-methylenedioxyamphetamine (MDA) and the A-methyl and A-ethyl analogues of the drugs were derivatized, with 4-chloroamphetamine being used as the internal standard. For powders, solutions were prepared at concentrations of 1 mgml in methanol and a 100 til aliquot blown dry under nitrogen. To the residue was added 50 p.1 of 0.5 M KOH and 500 p,l of toluene. The mixture was then shaken for 30 s and centrifuged, after which the toluene layer was recovered and HFBA (5 til) added. The excess reagent was neutralized with 500 p,l of 10% NaHCOs and an aliquot (1 ttl) analysed by GC-MS. Each of the amphetamines and the A-alkylated derivatives could be separated and identified on the basis of retention index and mass spectral data. 

Amphetamine derivatives are often misused as stimulants, particularly methylenedioxyamphetamines (MDMA, XTC, Ecstacy ). Immunoassays are available for screening, but confirmation of positive results must be performed by MS. The GC-MS requires derivatization. Therefore, LC-MS has been investigated... 

Methamphetamine often serves as the parent compound for synthesis of new designer drugs (Bost 1988 Buchanan and Brown 1988). Currently, one of the more popular designer drugs is MDMA, also known as ecstasy. MDMA is the methylated derivative of the amphetamine analog methylenedioxyamphetamine (MDA), a prototype of the hallucinogenic amphetamine drugs (Bost 1988). MDMA is relatively easy to synthesize... 

In these amphetamine derivatives, the hallucinogenic effects are predominant, exceeding those of the phenylethylamines many times over. Thus, for example, 2,5-dimethoxy-4-methylamphetamine (DOM) has approximately 100 times the effect of mescalin [11]. Its effects of serenity, tranquility, and peace give the product its scene name STP . All substances, including 3,4,5-trimethoxy-amphetamine (TMA), which is also a metabolite of elemicine (a constituent of nutmeg), and 4-bromo-2,5-dimethoxyamphetamine (DOB), have been almost completely displaced by the methylenedioxyamphetamines and today play an insignificant role in the drug scene. 

Several people have asked me what I thought about the potential activity of a compound with a methyl group added to DMMDA. One of these possibilities would be the N-methylated derivative, 2,5-dimethoxy-N-methyl-3,4-methylenedioxyamphetamine, or METHYL-DMMDA (or... 

The retention characteristics of sixteen phenylalkylamine derivatives (e.g., amphetamine, phentermine, 5-methoxy-3,4-methylenedioxyamphetamine, mescaline, methoxamine) were monitored on a 40°C C g column (photodiode array detector, A= 190-300nm) using a complex 22-min 5.5/94.5-> 39/61 (90/10 acetonitrile/water [5mL/L H3PO4 and 0.28 mL/L hexylamine])/water (5mL/L H3PO4 and 0.28 mL/L hexylamine) gradient [1425]. Urine and cactus samples were extracted and detection limits of 25-50 ng/mL and 40ng/g, respectively, were reported. 

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