Amfetamine structure

Although it resembles amfetamine structurally, the appetite suppressant fenfluramine does not produce central nervous system stimulation in therapeutic doses. 

Modafinil contains a diphenylmethyl moiety and hence is traly dissimilar from the amfetamine structure. The (R)-enantiomer of modafinil appears to sustain higher... 

Tranylcypromine is a non-hydrazine monoamine oxidase (MAO) inhibitor with actions and uses similar to those of phenelzine, but with less prolonged inhibition. Its half-life is 90-190 minutes. It is structurally related to amfetamine, to which it is metabolized in overdose (1). 

Four cases of addiction to tranylcypromine have been described, in addition to the three reported since 1965 (2). The dosage was 150-300 mg/day. The mild euphoriant properties of tranylcypromine reflect its structural resemblance to amfetamine, and probably account for tolerance and addiction in predisposed individuals. Tranylcypromine abuse in 18 patients has been reviewed (3), and two further reports have appeared (SEDA-17,17) (4). In one case (5), the patient took 440 mg/day without any adverse effects. The patient reported that she was longing for the energizing effect of the drug and for the feeling of freedom and power. Withdrawal resulted in repeated generalized seizures and status epilepticus. 

The major effects of khat on the central nervous system can be attributed to cathinone (S-(-)-alpha-aminopro-priophenone) in fresh khat leaves and cathine (norpseu-doephedrine) in dried khat leaves and stems. Cathinone, a phenylalkylamine, is the major active component and is structurally similar to amfetamine. It degrades to norp-seudoephedrine and norephedrine within days of leaf picking. Cathinone increases dopamine release and reduces dopamine re-uptake (1). 

Amfetamine has had multifarious uses. It is now obsolete for depression and as an appetite suppressant, and its use in sport is abuse (see before). There is concern that its illicit use as a psychostimulant is widespread. Amfetamine is a racemic compound the laevo-form is relatively inactive but dexamphetamine (the dextro- isomer) finds use in medicine. Amfetamine will be described, and structurally-related drugs only in the ways in which they differ. 

Anorectic drugs act mainly on the satiety centre in the hypothalamus (1). They also have metabohc effects involving fat and carbohydrate metaboUsm. Most of them are structurally related to amfetamine and increase physical activity. Their therapeutic effect tends to abate after some months, and part of this reduction in effect may be due to chemical alterations in the brain. Fenfluramine commonly produces drowsiness in normal doses, but has stimulaut effects in overdosage. Dexamfetamine, phenmetrazine, and benzfetamine all tend to cause euphoria, with a risk of addiction. Euphoria occasionally occurs with amfepramone (diethylpropion), phentermine, and chlorphentermine, but to a much lesser extent. Some adverse effects are due to sympathetic stimulation and gastrointestinal irritation these may necessitate withdrawal but are never serious. There are interactions with monoamine oxidase inhibitors and antihypertensive drugs. 

Phentermine is a central nervous system stimulant that can increase brain dopamine concentrations and has a structure similar to amfetamine. 

Fenproporex, one of the lesser known anorectic drugs, is structurally related to amfetamine, to which it is rapidly metabolized after oral ingestion. Stimulatory effects, somnolence, and electroencephalographic abnormalities are reported to be the major undesired reactions (1). 

Prolintane, an amfetamine-related substance, is a central nervous system stimulant with similar structure and properties to dexamfetamine. Prolintane hydrochloride is available mainly in many formulations with multivitamin supplements in many European countries, Australia, and South Africa. 

The dosage was 150-300 mg/day. The mild euphoriant properties of tranylcypromine reflect its structural resemblance to amfetamine, and probably account for tolerance and addiction in predisposed individuals. Tranylcypromine abuse in 18 patients has been reviewed... 

Amfetamine (Fig. 10.15) has structural similarities to noradrenaline. In the form of the free base it is relatively volatile and was thus used as a nasal decongestant through promoting constriction of mucosal blood vessels. It also has appetite-suppressing effects which have been attributed to its ability to displace serotonin from synaptic vesides, but since noradrenaline increases blood sugar levels this may also be part of its action. It is not fre-quendy used because of it potential for being addictive since, because of its high lipophilidty, it can also enter the CNS. Its main indication in current practice is in the treatment of narcolepsy. Amfetamines are discussed in more detail in Chapter 18. 

Modafinil (Fig. 18.12) is also a non-amfetamine with psychostimulant properties, used for the treatment of narcolepsy, ADHD, obstruaive sleep apnea/hypopnea syndrome and may show potential for the treatment of cocaine withdrawal symptoms. Inspection of the structural representation indicates that modafinil contains a diphe-nylmethyl moiety and hence is dissimilar from an... 

Methylphenidate (Ritalin) is a behavioural stimulant used for the treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD). It is commonly classified as a non-amfetamine but its nucleus is still present in that structure. The erytliro-racemate, i.e. (2 R,2"S)- and (2 S,2"R)-methylphenidate, shows negligible stimulant activity and is not used. The racemic threo-mcemate is responsible for activity but the (2 R,2"R)-enantiomer (dexmethylphenidate) displayed a more powerful inhibition of catecholamine uptake. 

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. 

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