Cocaine Amfetamines

Adverse effects of catecholaminergic stimulants, such as amfetamine and cocaine, fall into several categories, based on dose, time after dose, chronicity of use, and pattern of use/abuse (for example 4-5 day bingeing episodes). Adverse effects include not only responses during the period of use but also intermediate and longterm residual effects after withdrawal. For example, in some abusers once an amfetamine psychosis has developed with chronic abuse, only one or two moderate doses are required to induce the full-blown psychosis in its original form, even long after withdrawal (1). This is also evidenced by the precipitous slide to severe re-addic-tion in former abusers who are re-introduced to stimulants. 

A previously healthy 16-year-old schoolboy had mesencephalic ischemia, most probably caused by vasospasm, after combined abuse of amfetamine and cocaine (51). There was a close temporal relation between intake of the drug and the onset of symptoms. Thus, combining these drugs, even in small amounts, may be harmful. 

A previously healthy 16-year-old man developed an unsteady gait and double vision. His symptoms began 5 minutes after intranasal amfetamine (actually amfetamine cut with cocaine). He had a left-sided internuclear ophthalmoplegia, an incomplete fascicular paresis of the left oculomotor nerve, and saccadic vertical smooth pursuit. Cranial MRI showed a leftsided hyperintense lesion near the midline of the mesencephalon. A repeat MRI scan 9 days later showed that the lesion was much smaller. He made a full recovery within 3 weeks. 

The psychotropic effects of cocaine are similar to those of amfetamine (euphoria and excitement) but briefer and are due to blockade of the reuptake of dopamine at central nervous system synapses, which increases its concentration at receptors and produces the characteristic high. ... 

Possession and supply illegal except by Home Office Licence Drugs of high abuse potential with medicinal use, opiates and major stimulants, for example amfetamines and cocaine Subject to full controlled drug requirements under the law Drugs of lesser abuse potential with medicinal use for example minor stimulants and barbiturates Subject to special prescription requirements, but not other requirements under the law Anabolic steroids and related hormones Most benzodiazepines and zolpidem Subject to minimal control requirements Sale and supply and possession without a prescription for personal use an offence... 

Class A All opiates, hallucinogens, cocaine, injectable amfetamines, cannabinol and coca leaf Class B Amfetamines, codeine, pholcodeine and barbiturates Class C Milder stimulants and tranquilizers, benzfetamine, benzodiazepines, cannabis and anabolic steroids and related hormones... 

A 16-year-old boy developed unsteadiness and double vision 5 minutes after intranasal inhalation of a small amount of amfetamine cut with cocaine. Cranial MRI (magnetic resonance imaging) revealed a mesencephalic lesion that was seen to have decreased 12 days later, and he became symptom-free after 3 weeks. The ischaemic lesion was thought to be due to vasospasm caused by synergistic stimulation of the sympathetic nervous system amfetamine causes the release of adrenaline (epinephrine) and noradrenaline (norepinephrine), while cocaine prevents their reuptake. ... 

An example of a non-amfetamine behavioural stimulant is methylphenidate (Ritalin) (Fig. 18.11) and, correspondingly, it is used for the treatment of ADHD and narcolepsy. It shows both a direct cocaine-like action via dopamine... 

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... 

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. 

---