Amphetamine derived hallucinogen

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. 

The active drug and metabolites can be detected from the urine by thin-layer chromatography, gas-liquid chromatography, or gas chromatography-mass spectrometry. However, assays are available only at specialized centers. Treatment of acute intoxication with mescaline is virtually identical to the treatment outlined for LSD intoxication. DOM-induced vasospasm responds well to intra-arterial tolazohne or sodium nitroprusside. Major life-threatening complications of hallucinogenic amphetamine derivatives include hyperthermia, hypertension, convulsions, cardiovascular collapse, and self-inflicted trauma. 

In low doses nutmeg, which contains 30-40% fat and 10-15% essential oil, is an excellent spice. The main ingredients of the essential oil are terpenes and also the substances myristicin and elemicin. Both substances are pharmacologically inactive, but in the human body they are partly transformed into amphetamine-derivatives, which have a hallucinogenic action. This action is seen after intake of large amounts of nutmeg. 

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. 

While the majority of studies have focused on LSD, some evidence suggests that hallucinogens derived from the phenylethylamine nucleus affect locomotion in a manner that is interpretable only by considering the environmental context. For example, the substituted amphetamine DOM produces a dose-dependent (0.5-10 mg/kg) reduction in locomotor activity when rats are tested in a novel open field, while a slight but significant increase in activity is observed in a familiar environment (171). This report corroborates the separate findings of DOM-induced hyperactivity in rats or mice in a familiar chamber (29,196) and hypoactivity in mice in an unfamiliar setting (92). Mescaline (10 mg/kg) has also been reported to increase locomotion in rats in a familiar environment (196). 

While mescaline is a simple 2-phenethylamine derivative, the addition of an alpha-methyl group to the side chain yields Structure 8 (TMA). This simple hybrid of the structures of mescaline and amphetamine retains the hallucinogenic effects of mescaline but possesses about twice the potency of the latter (174,200). Addition of the alpha-methyl to other 3,4,5-substituted compounds generally brings about an approximately twofold increase in potency. The addition of an alpha-methyl to 2,4,5-substituted compounds, however, may dramatically increase activity. For example, 2-(2,4,5-trimethoxyphenyl) ethylamine apparently is clinically inactive (195). Addition of an alpha-methyl gives TMA-2 (Table 1), with 20 times the potency of mescaline. However, the addition of an alpha-methyl does not significantly increase in vitro receptor affinity in either 3,4,5-or 2,4,5-series (72,78). Thus it is probable that the alpha-methyl may confer metabolic stability in vivo. It could also be speculated that this protection is more important in the 2,4,5-substituted series than in 3,4,5-substituted compounds. 

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

However, MPPP is sometimes contaminated with the side reaction product l-methyl,4-phenyl-l,2,3,6-tetra-hydropyridine (MPTP), which produces a parkinsonian syndrome through nigrostriatal lesions. Several substituted derivatives of amphetamine have also been called designer drugs. The most widely known of this group is the hallucinogen MDMA (ecstasy). 

B. A. O Brien, J. M. Bonicamp, and D. W. Jones, Differentiation of amphetamine and its major hallucinogenic derivatives using thin-layer chromatography, J. Anal. Toxicol., 6 143 (1982). 

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. 

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... 

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