Cocaine properties

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

To summarize the data in table 1, neither MDMA nor MBDB has hallu-cinogen-like discriminative stimulus properties. Symmetrical transfer of the MDMA and MBDB stimulus indicates that their primary discriminative stimulus effects are very similar. For both MDMA and MBDB, there is enantioselectivity for the S isomer, with about a twofold eudismic ratio. Finally, the substitution of (- )-amphetamine and cocaine in MDMA-trained rats may indicate that MDMA has some psychostimulant-like properties, while hffiDB seems to lack this activity. 

Chemical Structures. Figure 1 shows the chemical structures for 14 phenylethylamine compounds. Nine of these compounds are used clinically as anorectics (ii-amphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, clotermine, chlorphentermine, benzphetamine, and fenfluramine). Four of these compounds are not approved for clinical use and are reported to have hallucinogenic properties (MDA, PMA, DOM, and DOET). The final compound ( /-ephedrine) is used clinically for bronchial muscle relaxation, cardiovascular, and mydriatic effects. Figure 2 shows the chemical structure for MDMA, the methyl analog of MDA. MDMA is not approved for clinical use and has been reported to produce both LSD-like and cocaine-like effects. 

The pharmacological properties of phenylethylamines that control selfadministration are complex. The effects of phenylethylamines on a variety of pharmacological measures do not appear to predict the reinforcing effects of these drugs, as measured by the cocaine substitution procedure in primates. Specifically, none of the following behavioral effects of these compounds accurately predict the results of self-administration experiments within the phenylethylamine class (Griffiths et al. 1976 Griffiths et al. 

Both amphetamine and cocaine have also been reported to support intracranial self-administration in the mesolimbic/mesocortical dopaminergic system. Rats will self-administer cocaine into the medial prefrontal cortex (Goeders and Smith 1983). while amphetamine is self-administered into the orbitofrontal cortex of rhesus monkeys (Phillips and Rolls 1981) and the nucleus accumbens of rats (Hoebel et al. 1983 Monaco et al. 1981). These data indicate that the mesolimbic/mesocortical dopaminergic system is involved in the initiation of stimulant reinforcement processes, and this work suggests that the region of the nucleus accumbens, more specifically the mesolimbic dopamine system, may be an important substrate for reinforcing properties of several psychomotor stimulant drugs. 

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