Stimulants phenylisopropylamines

A closely related agent is PMMA, or N-methyl-1-(4-methoxyphenyl)-2-aminopropane. PMMA is a hybrid structure of two phenylisopropylamine stimulants PMA, and methamphetamine (Fig. 23.6) Surprisingly, PMMA lacks significant central stimulant actions, and unlike PMA and methamphetamine, PMMA is not recognized by (+)-amphetamine-trained animals. Because PMMA is structurally related to metabolites of MDMA, it was examined in MDMA-trained animals and found to be several-fold more potent than MDMA. Animals have been trained to discriminate PMMA from vehicle, and PMMA stimulus generalization occurred to ( )-MDMA and S-(+)-MDMA, but not to DOM,... 

Therapeutic Function Central stimulant Chemical Name (S)-a-methylbenzeneethanamine sulfate Common Name d-j3-phenylisopropylamine sulfate Structural Formula... 

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). 

Amphetamine is a racemic mixture of phenylisopropylamine (Figure 9-4) that is important chiefly because of its use and misuse as a central nervous system stimulant (see Chapter 32). Pharmacokinetically, it is similar to ephedrine however, amphetamine even more... 

These possible steric effects have been evaluated by an approach involving partition coefficients. In this way, an estimate of comparative lipophilicity can be made since this property is felt to influence the ease of membrane transport and thus eventual availability to the site of action. A number of psychotomimetic phenylisopropylamines have been studied in an octanol-water partition system, and the correlation of the resulting values, with central activity has provided a relationship that suggests an optimum lipophilicity for maximum biological activity (Barfknecht et al. 1975). These partition values have been correlated to serotonin receptor stimulation capability (Nichols and Dyer 1977) and have recently been extended to a number of phenethylamine compounds (Nichols et al. 1977). 

Amphetamine (racemic /3-phenylisopropylamine see Table 10-1) acts indirectly to produce powerful stimulant actions in the CNS and a and /3 receptor stimulation in the periphery. Unlike Epi, amphetamine is effective after oral administration, and its effects last for several hours. 

Atropine will prevent the normal reflex bradycardia, since that requires integrity of the vagal pathway. The direct action of norepinephrine on the sinus node wiU be unmasked. The answer is (C). Phenylisopropylamines such as amphetamine are traditional stimulants with a spectrum of effects from mild alerting to paranoid schizophrenia and convulsions antimuscarinic agents are capable of inducing hallucinations and convulsions. The answer is (C). 

Other methyl-substituted phenylethylamines (phenylisopropylamines). such as (S)-(+)-amphetamine and (S)-(+)-methamphetamine, which lack both ring substituents I side-chain hydroxyl, are sufficiently lipophilic to cross the blood-brain barrier readily and cause dramatic CNS stimulation, which gives them serious abuse... 

Bupropion (amfebutamone) is a phenylisopropylaminoketone that is structurally related to the phenylisopropylamine CNS stimulant, methamphetamine, and the phenylisopropylaminoketone, cathinone (a constituent in khat), and the anorexiant, diethylpropion (Fig. 21.21). Although structurally similar to the CNS stimulants, bupropion exhibits distinctive different pharmacologic and therapeutic effects. The absence of the tricyclic ring system in bupropion results in a better adverse-effect profile than with the TCAs. The tertiary butyl group in bupropion prevents its N-dealkylation to metabolites that could possess sympathomimetic and/or anorexigenic properties. 

The term stimulant typically conjures up substances such as the phenylisopropylamine amphetamine and the tropane analogue cocaine. The following discussion will focus primarily on such substances. 

The simplest unsubstituted phenylisopropylamine is 1-phenyl-2-aminopropane, or amphetamine. Amphetamine possesses central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this ciass (33). It is common to refer to amphetaminergic structures and amphetaminergic activity, but amphetamine may be more of an exception than a rule. Most substituted derivatives of amphetamine (i.e., phenyiisopropyiamine) lack central stimulant activity in fact, pharmacologically, there are a greater number of non-amphetamine-like derivatives of amphetamine than there are amphetamine-like derivatives of amphetamine. Relatively few derivatives of amphetamine retain the activity of amphetamine still fewer retain the potency of amphetamine. The present section will focus almost exclusively on the central stimulant actions of amphetamine, and it should be recognized that these SARs are not necessarily identical to those for anorectic or sympathomimetic actions. 

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