Amfetamine derivatives

Mescaline is one of eight hallucinogenic alkaloids derived from the peyote cactus, slices of which ( peyote buttons ) have been used in religious rites by North and South American Indian tribes. Mescaline itself is only one of the alkaloids present in peyote, but it produces the same effects as the crude preparation. Chemically, it is related to amfetamine. In doses of some 300-500 mg it depresses nervous system activity and produces visual and occasionally auditory hallucinations, illusions, depersonalization, and depressive symptoms (1). The total picture can closely resemble that caused by lysergic acid diethylamide. Its physical effects include nausea, tremor, and sweating. 

Osmotic-release oral system Polymerase chain reaction P aramethoxy amfetamine P aramethoxymetamfetamine Peroxisome proliferator-activated receptor Parts per billion Purified protein derivative Parts per million See HbOC... 

Amfetamine (Fig. 18.4) is often named as a representative example for an indirect dopamine-releasing psychostimulant. The presence of the P-phenylethylamine nucleus is a common theme in a variety of psychoactive derivatives. CNS activity and adverse reactions typically found with amfetamines are shared by most psychostimulants, albeit to a different degree and intensity. Amfetamine itself can be used safely, provided that dose and route of administration are followed as prescribed for a particular condition. The two most common areas of application include narcolepsy and ADHD. 

Fenetylline is an interesting example where the molecule consists of a combination of sympathomimetic-like entities. In this compound the caffeine derivative theophylline is fused to amfetamine and it has been used for the treatment of ADHD and narcolepsy. It has been claimed that fenetylline showed fewer amfetamine-type side effects such as elevated blood pressure, tremor and fine motor activity, but became ill al due to increased numbers of abusers. A typical adult dose of fenetylline hydrochloride is 25-50 mg once or twice a day. Fenetylline abuse has been reported to be particularly prominent in the Middle East and a large number of counterfeit products are circulating. 

Bupropion hydrochloride f/c tablets 150 mg. Adult dose 150-300 mg for 7-9 weeks (smoking cessation). In severe cases of depression, up to 450 mg of the hydrochloride salt have been recommended. Diethylpropion (diethylcathinone) is the N,N-diethyl derivative without the presence of the chlorine atom and displays amfetamine-like effects in humans. When... 

Ephedrine derivatives may be viewed as hybrids between amfetamines and adrenergic drags. They lack the 3,4-dihydroxylated component but retain the presence of the P-hydroxyl group on the side chain, thus attenuating stimulatory pharmacology. Ephedrines have two chiral centres which give rise to four stereoisomers. The naturally occurring ephedrine is identifiable as the (lR,2S)-stereoisomer. The (lS,2S)-stereoisomer is known as (lS,2S)-cathine or (lS,2S)-pseudonorephedrine. 

Cocaine is a tropane-type derivative with several chiral centres and only the (lJ ,2f ,3S,5S)-stereoisomer, also called (—)-cocaine, appears to have appreciable psychostimulant properties. Its primary mode of action is based on blockage of the dopamine transporter which is defined as a directly mediated mechanism. Cocaine is therefore classified as a dopamine blocker rather than dopamine releaser, as is the case with some amfetamines. A large number of 2P,3P-cocaine analogues are well tolerated by the dopamine transporter but not necessarily by the noradrenaline or serotonin counterparts. This means that dopamine reuptake blockage alone is not necessarily sufficient to reinforce consumption, and appropriate stmctural modifications could lead to the development of treatment options for cocaine abuse. 

Sibutramine is also a mixed inhibitor of SERT and NAT but does not display any antidepressant properties. Instead, it is used in the management of obesity, following an observed reduction of food intake. Structurally, one can observe the substituent at the a-carbon, in this case an isobutyl group, which gives an amfetamine-type derivative. 

The previous section on CNS stimulants described the fact that amfetamine and its N-methylated derivative show stimulatory properties. This was attributed to the lack of... 

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