Amphetamines structure

QUESTION You seemed to have looked through all of the various substituents in your amphetamine structure, with one exception. You did not touch the benzene ring itself What would happen if you saturate the benzene ring and make a saccharide derivative of amphetamine ... 

Amphetamines are definitely drugs which have been and are abused. Notice that the organic modifications in the fundamental amphetamine structure are to make the compound more lipophilic and so speed its delivery to the CNS as well as heighten the stimulant and euphoric effect. Therapeutic doses of amphetamines range from 5 to 10 mg for a maximum of 60 mg per day while abusive doses may be as high as 500-1000 mg every 2-3 hours. The side effects of abuse include tolerance, addiction, malnutrition, heart arrthymias, and... 

The psychedelic amphetamines are a fascinating and largely ignored group of drugs. They all have the basic amphetamine carbon skeleton structure, but show effects that are more akin to LSD than to the amphetamines. The LSD-like effect is due to the presence of a variety of "add ons" to the benzene ring of the basic amphetamine structure. 

Thus it may be concluded that in this group of compounds molecular modification of the amphetamine structure achieved a distinct selectivity of action with regard to psychomotor stimulation and a considerably lessened incidence of the usual amphetamine side effects such as anorexia, jitteriness, apprehension, cardiovascular effects, insomnia, tolerance, and postdrug depression. 

Snyder, S. H., Richelson, E., Weingartner, H. and Faillace, L. A. (1970). Psychotropic methoxy-amphetamines. Structure and activity in man. In Amphetamines and Related Compounds, E. Costa and S. Garratini (Eds.), Raven Press, New York, pp. 905-928. 

Fenfluramine (No. 13) is unique among amphetamine-type anorexiants. In spite of its amphetamine structure and the presence of the highly lipophilic m-CF3 group, this compound possesses a sedative rather than CNS stimulatory effect. The drug has been shown to cause serotonin depletion. Serotonin (and NE) are involved in sleep regulatory mechanisms. Thus a relationship seems possible. 

The ecstasy molecule itself is just an amphetamine with a couple of extra things attached to it. The chemical structures of the major ecstasy class drugs and speed class drugs can be seen in the preceding schematic ... 

Structural Formula A complex of amphetamine, C HsCHjCHlCHsiNHj and tannic acid Chemical Abstracts Registry No. 1407-85-8... 

On the other hand, because enantiomers differ in their three-dimensional structure, they often interact with biochemical molecules in different ways. As a result, they may show quite different physiological properties. Consider, for example, amphetamine, often used illicitly as an upper or pep pill. Amphetamine consists of two enantiomers ... 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

The amphetamine-like properties of trace amines are best described for PEA which shares close structural similarity to amphetamine and can displace monoamine neurotransmitters from synaptic vesicles and trigger their release into the synaptic cleft by acting on the dopamine transporter. However, this effect is only observed at high, supra-physiological PEA concentrations and thus might not occur under physiological conditions. 

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... 

The phenylalkylamine hallucinogens show a close structural resemblance to the catecholamines, noradrenahne and dopamine. The prototype structure is found in mescaline, a naturally occurring substance. Modification of the mescaline molecule has led to synthetic amphetamine derivatives with hallucinogenic action. 

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. 

Thus, for this class of psychoactive agent, prehminary structure-activity relationships are being formulated. Currently, four structural features eontrast the structure-activity relationships of entactogens with those of hallueinogenie amphetamines. 

Recent controversy about the recreational abuse and potential therapeutic use of designer drugs has focused attention on MDA (methylenedioxyampheta-mine HCl) and structurally related phenylisopropylamine compounds, including MDMA istructural analogs of the psychomotor stimulant amphetamine and the hallucinogen mescaline, and produce stimulant and/or hallucinogenic effects (Shulgin 1978). 

Chemical Structures. Figure 1 shows the chemical structures for 14 phenylethylamine compounds. Nine of these compounds are used clinically as anorectics (ii-amphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, clotermine, chlorphentermine, benzphetamine, and fenfluramine). Four of these compounds are not approved for clinical use and are reported to have hallucinogenic properties (MDA, PMA, DOM, and DOET). The final compound ( /-ephedrine) is used clinically for bronchial muscle relaxation, cardiovascular, and mydriatic effects. Figure 2 shows the chemical structure for MDMA, the methyl analog of MDA. MDMA is not approved for clinical use and has been reported to produce both LSD-like and cocaine-like effects. 

Woolverton, W.L. Shybut, G. and Johanson, CE. Structure-activity relationships among some t(-N-alkylated amphetamines. Pharmacol Biochem Behav 13 869-876, 1980. 

AMPHETAMINE-LIKE STRUCTURE-ACTIVITY RELATIONSHIPS Aromatic Substituents... 

Young, R., and Glennon, R.A. Discriminative stimulus properties of amphetamine and structurally related phenalkylamines. Med Res Rev 6 99-130, 1986. 

Characteristic of its amphetamine-like structure, MDMA is a potent monoamine-releasing agent as demonstrated both in vitro (Nichols et al. 1982 Johnson et al. 1986 Schmidt et al. 1987) and in vivo (Yamamoto and Spanos 1988). This release occurs through a carrier-mediated, Ca -independent mechanism typical of the phenethylamines (Schmidt et al. 

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