Amphetamine analogs

G.K.W. Effects of certain hallucinogenie amphetamine analogs on the release of [ H]serotonin from rat brain synaptosomes. J Med Chem 25 530-535, 1982. 

Glennon, R.A. Synthesis and evaluation of amphetamine analogs. Proceedings of the Joint WHO/Drug Enforcement Actoinistration Conference on Controlled Substance Analogs. Rabat, Morocco, September, 1987b. 

FIGURE 6. Elution pattern of monoamine uptake blockers and amphetamine analogs from reverse-phase HPLC... 

Effects of Amphetamine Analogs on Central Nervous System Neuropeptide Systems... 

This chapter discusses the responses of these extrapyramidal neuropeptide systems to the amphetamine analogs methamphetamine (METH), methylene dioxyamphetamine (MDA), and methylenedioxymethamphetamine (MDMA). These dmgs were selected for this study because they represent somewhat diverse mechanisms of action. While all three agents are able to enhance extrapyramidal serotonergic activity (Schmidt et al. 1987). only METH has been characterized as a substantial stimulant of the DA system. The effects of MDA and MDMA on extrapyramidal DA systems have not been well elucidated. Thus, evaluating and comparing the responses of the SP, NT, and Dyn extrapyramidal systems to these dmgs will help to determine the nature of the DA responses to METH, MDA, and MDMA administrations. 

These findings demonstrate that some neuropeptide systems associated with mesostriatal dopaminergic projections are profoundly altered by treatment with each amphetamine analog examined.Although the signifieanee of these drug-induced increases in striatal and nigral eontents of SP, NT, and... 

Dyn is not yet known, it is likely that such changes reflect variations in the activity of the associated pathways. One possible explanation is that increases in neuropeptide tissue levels are due to decreased release of the transmitter, which dunmishes the extracellular peptide metabolism and results in accumulation of these peptide substances. Another possible contributing factor is a drug-related alteration in neuropeptide synthesis. For example, Bannon et al. (1987) reported that METH administration increased the quantity of striatal messenger RNA for the SP precursor preprotachykinin. Thus, increases in peptide synthesis might contribute to increases in peptide content caused by treatment with METH or the other amphetamine analogs. 

This volume has focused on several amphetamine analogs in addition to amphetamine and methamphetamine, especially 3,4-methylenedioxymeth-amphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA). 

Possible Role of an Active Metabolite of the Drug in the Neurotoxicity of Amphetamine Analogs... 

The possibility that an aetive metabolite is involved in the neurotoxic effects of amphetamine analogs reeeives limited discussion in this chapter and has been considered previously, espeeially with />-chloroamphetamine (Miller et al. 1986.) Partly beeause the ehemieal structures of these amphetamines do not suggest ways in whieh they would be toxic to neurons, the... 

A fourth approach to evaluating the intactness of dopamine and/or serotonin neurons in human subjects who have taken one of the amphetamine analogs might be to use a probe for labeling a constituent of those neurons in position emission tomography scanning studies. A label for the serotonin or dopamine uptake carrier, or a label for tryptophan hydroxylase or tyrosine... 

Weintraub, H. J. R., and Nichols, D. E. (1978) Conformational energy calculations of some amphetamine analogs using a new solvation model. Int. J. Quant. Chem., QBS 5 321-343. 

Cheng, H. C., Long, J. P., Nichols, D. E., Barfknecht, C. F., and Rusterholz, D. B. (1974) Effects of rigid amphetamine analogs on vascular strips Studies of 2-aminotetrahydronaphthalene and 2-aminoindane derivatives. Arch. Int. Pharmacodyn. Ther., 208 264-273. 

Shulgin, A. T., Sargent, T., and Naranjo, C. (1971) 4-Bromo-2,5-dimethoxyphenylisopropyl-amine, a new centrally active amphetamine analog. Pharmacology, 5 103-107. 

MDMA s history dates to the early years of the 20th century when researchers at the German pharmaceutical company Merck discovered the compound and a number of related amphetamine analogs, including 3,4-methylenedioxyamphetamine (MDA) and 3,4-methyl-enedioxy-N-ethylamphetamine (MDEA). Merck s research began as an attempt to discover a substance that could be used as a vasoconstrictor, a substance that causes a narrowing of blood vessels and can be used to reduce bleeding. 

The amphetamine analog of CPM should be easily made from the alkylation of syringaldehyde with cyclopropyl chloride, followed by conventional reaction of the resulting aldehyde with nitroethane, and finally a reduction step. There is no reason to believe that the resulting compound 3,5-dimethoxy-4-cyclo-propyloxyamphetamine (3C-CPM) would be any shorter acting than CPM. 

D. Wu, V. Otton, T. Inaba, W. Kalow, E. Sellers, Interactions of Amphetamine Analogs with Human Liver CYP2D6 , Biochem. Pharmacol., 53,1605-1612 (1997). 

The amphetamines were replaced by amphetamine analogs—substances somewhat less potent than amphetamines. Fen-Phen, the combination of fenfluramine and phentermine, was a popular appetite suppressant in the 1990s, but was associated with severe health problems such as pulmonary hypertension, heart valve dysfunction, and nerve damage. As a result, both drugs were withdrawn from the market. 

Nitiyl iodide, from iodine vdth ver nitrite or from NO2 and iodine, adds to alkenes, generally in ether at room temperature, by a radical mechanism. Yields are 50-90%. The products yield nitroalkenes on treatment wiA base, a sequence used recently in the preparation of intermediates (Aidi=CMeN02) for amphetamine analogs. The reaction is also a key step in the a-methylenebuty-lolactone synthesis shown in Scheme 88. ... 

The decalin amphetamine analogs (skeleton 1 in Table V) were tested for their effect on motor activity (86), since amphetamine itself is known to increase motor activity. Paradoxically, all four compounds decreased motor activity. In addition, the extended conformer caused lachrymation. Later studies (87,88,89) on... 

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