Amphetamine studies

Amphetamines can be determined in hair by a GC-MS method following SFE (103). Flair was washed sequentially with sodium docecyl sulfate (SDS), CF12C12, methanol, and water and then dried. The amphetamines were extracted from the hair with 90% CO2 and 10% CFlCls/isopropyl alcohol at 262 bar and 70°C as the extractant in the dynamic extraction mode for 30 min. The amphetamine were derivatized and determined by GC MS. Mephenter-mine was used as an internal standard. The calibration graphs were linear from 0.02 to 20 ng/mg for all of the amphetamines studied. The detection limits were 0.02-0.1 ng/mg, the RSDs (five replicates) were 11-28%, and the recoveries were 71-84%. 

Meyer MR, Wilhelm J, Peters FT, Maurer HH. Beta-keto amphetamines studies on the metabohsm of the designer mephedrone and toxicological detection of mephedrone, butylone and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 2010 397 1225-33. 

METHOD 2 This method is a backup use for all that bromo-safrole or phenylisopropyl-bromide that the chemist made. It is the simplest method in the entire book, uses the cheapest most basic ingredients and happens to be the first method that Strike ever studied [59]. Strike does not have many fond reminiscences about this method because it kind of sucks but the chemistry is so basic that it may well serve the most pathetic chemist. The reaction proceeds as follows which uses ammonia to replace the bromine giving MDA or amphetamine directly ... 

The postulation of a possible role of trace amines in the context of schizophrenia was kindled early on by the structural similarity between PEA and amphetamine. Symptoms such as hallucinations and paranoid episodes caused by a prolonged amphetamine intoxification are reminiscent of patients suffering from acute schizophrenia. Further support for a role of trace amines in the context of schizophrenia comes from clinical studies... 

More than 40 medications have been investigated but none have shown consistent efficacy for primary cocaine or amphetamine dependence. These medications include dopaminergic agonists, antidepressants, and more recently disulfiram, selegiline, and a cocaine vaccine (see Table 5—2 for summary). Studies have been relatively brief and have focused on abstinence initiation rather than on relapse prevention, but even these modest treatment goals have not been attained. The focus in the discussion that follows is on pharmacotherapies for cocaine dependence, because very few clinical trials have been completed with amphetamine-dependent patients. Furthermore, none of the studies of amphetamine dependence have shown results different from those described for cocaine dependence (Rawson et al. 2002b Srisurapanont et al. 2001). 

Although some studies show that noradrenaline inhibits neuronal firing it is generally considered to increase behavioural activity and arousal. This impression is borne out to the extent that CNS stimulants, like amphetamine, increase release of noradrenaline and produce behavioural and EEG arousal, while reserpine, which reduces noradrenaline storage and hence release, causes psychomotor retardation. It is also supported by... 

MDMA is believed to have unique psychoactive properties that clearly distinguish it from hallucinogenic or psychostimulant phenethylamines. Not only have MDMA users consistently reported this distinctiveness, but subsequent studies of MDMA and similar compounds, in many laboratories, have shown that they do not fit within the structure-activity relationships that presently are understood to define the hallucinogenic amphetamines. 

MDA had unique psychoactive properties that were different from hallucinogens such as LSD or mescaline. While MDA in high doses appears to be hallucinogenic or psychotomimetic, it seems not to have been used for this effect, but rather for its effects on mood production of a sense of decreased anxiety and enhanced self-awareness. Even early reports described the desire of MDA users to be with and talk to other people (Jackson and Reed 1970). MDA is also the only substituted amphetamine that received serious clinical study as an adjunct to psychotherapy (Yensen et al. 1976). 

In earlier proposals (Anderson et al. 1978), based on this stereoselectivity for the S enantiomer of MDMA, it was suggested that, rather than having a direct effect at serotonin receptors, perhaps MDMA was a neurotransmitterreleasing agent, acting in a fashion similar to amphetamine, for which the S enantiomer is also more active than the R enantiomer. A subsequent study... 

These data clearly illustrate the enantioselectivity of the (-l-)-isomers of MDA, MDMA, and MBDB in producing an MDMA-like stimulus and underscore the fact that in vitro studies of the biochemical pharmacology of these substances should reveal similar selectivity, once the primary pharmacological process underlying the interoceptive cue is identified. The data also indicate that (-l-)-MDA is the most potent of all the drugs tested in MDMA- or in (-t)-MBDB-trained animals. The faet that (-l-)-MDA does not substitute in amphetamine-trained animals in our studies supports the argument that the pharmacology of this enantiomer of MDA is MDMA-like and is not like amphetamine. 

In view of the apparent pleasurable effects of MDMA, it becomes of considerable interest to understand the mechanism of action of substances with a similar effect. Major efforts have been directed toward the study of agents that have an effect on serotonin pathways, since that is the neurotransmitter system that seems most implicated in the mechanism of action of MDMA. This hypothesis is further reinforced by the observation that MDMA substitutes for fenfluramine (Schechter 1986). and fenfluramine substitutes for MBDB (Oberlender and Nichols, unpublished). The substitution data for (+)-amphetamine and cocaine in (-t-)-MBDB-trained rats are also similar to the data for substitution of these agents in fenfluramine-trained rats (White and Appel 1981). 

Another study underway has begun to examine the effect of paramethoxy-amphetamine (PMA) in MDMA-trained rats. After testing a few doses, it appears that full substitution may occur and that the S enantiomer of PMA... 

Oberlender, R., and Nichols, D.E. Drug discrimination studies with MDMA and amphetamine. Psychopharmacology (Berlin) 95 71-76, 1988. 

In a summary of the human abuse literature on anorectic phenylethylamines, Griffiths et al. (1979) found there was a good correlation between the results of self-administration studies in animals and information about the subjective effects and abuse in man. Specifically, amphetamine, diethyl-propion, and phenmetrazine have been associated with numerous clinical case reports involving abuse, and these three compounds as well as benz-phetamine and /-ephedrine have shown similar subjective effects in drug abuser populations (Griffiths et al. 1979). In addition, fenfluramine was associated with low incidence of abuse in humans and did not maintain self-injection responding in animals. Chlorphentermine was similarly associated with low incidence of abuse in man, but did not maintain selfinjection uniformly in animals (Griffiths et al. 1979). 

TABLE 2. Results of stimulus generalization studies using (+)amphetamine... 

QUESTION Is there any evidenee that a eommon effeet of amphetamine and MDMA is mediated through a common biochemical mechanism for example, antagonism studies in haloperidol ... 

The early report by Bradley (1937) on beneficial treatment effects with amphetamine in aggressive, destructive, irritable, and hyperactive boys was repeatedly eonfirmed by double-blind, placebo-controlled studies. Significant reductions in aggressive behavior and improvements in social interactions were found after treatment with 10 to 40 mg/day of d- or /-amphetamine for boys and girls, 5 to 14 years of age, who had been diagnosed as... 

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