Sensing cocaine

Fig. 37 (a) QD-based sensing of cocaine by the formation of a cocaine-aptamer supramolecular structure that triggers FRET and (b) time-dependent luminescence spectra of the system in the presence of cocaine. The inset shows a calibration curve for variable concentrations of cocaine and a fixed so observation time of 15 min. (c) Schematic of the FRET-based TNT sensor and (d) increase of the QD luminescence upon addition of TNT in the competitive assay format. (Reprinted with permission from [220, 221], Copyright 2009 Royal Society of Chemistry and 2005 American Chemical Society)... 

Temperature reduction generally provides a severalfold enhancement of nonequivalence magnitude (15,16,19). Cocaine (3) at 20°C shows methylphenylcarbinol-induced nonequivalence in Hj and Hj, and in the A-methyl and 0-methyl resonances of 0.14, 0.03, 0.01, and 0.05 ppm, respectively (15). On lowering the temperature to -40°C, these differences increase to 0.47, 0.06, 0.12, and 0.17 ppm. Only the nonequivalence for Hs changes in sense (zero nonequivalence is observed for H5 at 0°C). Although the increase in nonequivalence magnitude with a reduction of temperature can be attributed in some cases to an increase in the equilibrium constants for CSA-solute association, such enhancement is observed even when the CSA is present in such excess as to cause essentially complete solvation of the enantiomeric solutes (doubtless 3 is such an example). Here, temperature reduction must also increase the intrinsic spectral differ-... 

The nonequivalence observed in cocaine (3) suggests two or more conformations the nonequivalences for the Hi and 0-methyl increase by a factor of about 3.3, Af-methyl by about 12, and a change in sense was observed for H5 (no nonequivalence at 0°C) on lowering the temperature from 20 to -40°C. 

Abuse. We have all heard the terms substance abuse, drug abuse, alcohol abuse, cocaine abuse, and so on. In one sense, any illicit use of a substance is abuse. For example, from the legal point of view, whenever someone smokes crack (even if it is the only time), (s)he has broken the law and abused cocaine. Likewise, if you borrow a prescription sedative or pain reliever from a friend, then you have similarly abused that medication. That is an appropriate use of the term in many cases, but this is not customarily the way that mental health specialists use the term. From our perspective, substance abuse involves a pattern of repeated use over time that results in problems in one or more areas. These include compromised physical health and well-being, legal proceedings, job status, and relationships as well as overall day-to-day functioning. 

The cocaine addict most often presents during withdrawal after a binge of cocaine use. Cocaine withdrawal is not life threatening and does not require medical intervention in the same sense as alcohol or opiate withdrawal. It is, however, associated with a profound depression that can render the addict suicidal for 24-48 hours. The crashing cocaine addict should be assessed for suicide risk and, if indicated, the patient should be monitored in an emergency psychiatric setting or may require a brief 1-2 day inpatient psychiatric admission until the withdrawal resolves and the suicide risk is relieved. 

The reason that the illicit use of these drugs is so difficult to curb is not only because they elevate vigilance, but also because they greatly enhance mental energy, elevate mood, increase physical strength, and maximize sexual potency. This sounds like a dream, in the metaphorical sense, and indeed, some actual dreams have these desirable qualities, but the stimulants do not produce otherwise dreamlike mentation even when they trigger psychoses. The similarities between dopamine and cocaine can be appreciated in figure 15.2. 

One of the more notorious and abused stimulants is cocaine, a natural product isolated from the South American coca plant, shown in Figure 14.25. Once in the bloodstream, cocaine produces a sense of euphoria and increased stamina. It is also a powerhd local anesthetic when applied topically. Within a few decades of its first isolation from plant material in 1860, cocaine was used as a local anesthetic for eye surgery and dentistry—a practice that stopped once safer local anesthetics were discovered in the early 1900s. 

Cocaine (Fig. 13—3) has two major properties it is both a local anesthetic and an inhibitor of monoamine transporters, especially dopamine (Fig. 13—4). Cocaine s local anesthetic properties are still used in medicine, especially by ear, nose, and throat specialists (otolaryngologists). Freud himself exploited this property of cocaine to help dull the pain of his tongue cancer. He may have also exploited the second property of the drug, which is to produce euphoria, reduce fatigue, and create a sense of mental acuity due to inhibition of dopamine reuptake at the dopamine transporter. Cocaine also has similar but less important actions at the norepinephrine and the serotonin transporters (Fig. 13—3). Cocaine may do more than merely block the transporter—it may actually release dopamine (or norepinephrine or serotonin) by reversing neurotransmitter out of the presynaptic neuron via the monoamine transporters (Fig. 13—4). 

FIGURE 13—4. Pharmacology of cocaine. Cocaine is a powerful inhibitor of the dopamine transporter. Blocking this transporter acutely causes dopamine to accumulate, and this produces euphoria, reduces fatigue, and creates a sense of mental acuity. Cocaine has similar but less important actions at the norepinephrine and serotonin transporters. 

Cocaine and other local anesthetics abolish not only the sensation of pain, but other special sensations, if they are suitably applied. Here also there is some selection. In the skin, they paralyze first the vasoconstrictor reaction, then progressively the sensations of cold, warmth, touch, tickling, pressure, pain, and joint sense. In the nose, they abolish the olfactory sense. On the tongue, they destroy the taste for bitter substances but have less effect on sweet and sour taste and none on salty taste. When cocaine is applied to the appropriate nerves, it is found that the centrifugal vagus fibers are paralyzed before the centripetal, vasoconstrictor fibers before vasodilator, bronchial constrictors before the dilators, etc. (Sollmann, 1944). 

This effect is not surprising Amphetamines are potent psychomotor stimulants. Whether sniffed, swallowed, snorted, or injected, they induce feelings of power, strength, exhilaration, self-assertion, focus, and enhanced motivation. Amphetamine intake causes a release of the excitatory neurotransmitters dopamine and noradrenaline (norepinephrine) in the central nervous system (CNS). The release of dopamine typically induces a sense of aroused euphoria that may last several hours unlike cocaine, amphetamine is not readily broken down by the body. After taking amphetamines, feelings are intensified, the need to sleep or eat is diminished, and the user may feel as though he or she can take on the world. ... 

Jack, a recovering cocaine user, recalled that when he smoked crack he experienced an intense rush of pleasure, an ecstatic feeling that he was on top of the world, and a sense of well-being. He felt completely satiated and had no interest in food or sex while he was using drugs. 

The MDA cluster is presented here as the first of five psychedelic clusters that are more exotic—at least in the sense of being used by fewer people than LSD, mescaline, marijuana and psilocybian mushrooms. It should be emphasized that now we begin to depart from consensus on what s truly "psychedelic. Effects from members of the MDA-duster can easily be likened, and thereby denigrated in the minds of many, to those of cocaine or amphetamine. Although the MDA-like compounds are increasingly popular, their subdued effects couple them with the subtlety of marijuana for some. 

Indirect sympathomimetics (B) in the narrow sense comprise amphetamine-like substances and cocaine. Cocaine blocks the norepinephrine transporter (NAT), besides acting as a local anesthetic. Amphetamine is taken up into varicosities via NAT, and from there into storage vesicles (via the vesicular monoamine transporter), where it displaces NE into the cytosol. In addition, amphetamine blocks MAO, allowing cytosolic NE concentration to rise unimpeded. This induces the plasmalemmal NAT to transport Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

At first, George Merck merely ran the American branch of dad s export business. However, in that era of high tariffs, he figured it would make sense to start manufacturing his own supply. In 1900 he bought some 120 acres of swamps and woodland in Rahway, New Jersey, for a manufacturing plant, followed by a factory in St. Louis. Among his products were iodides, bismuths, morphine, and cocaine—the last two considered medicines at the turn of the century. 

The most well-known drugs of abuse are heroin, cocaine, cannabis, LSD, amphetamines, and ecstasy. They all cause different kinds of effects and their toxic effects are also different. The first three of these are derived from or closely aUied to substances found in plants. LSD is similar to substances found in a fungus which affects crops (see pp. 244-7). h is appropriate to consider these substances here as they are drugs in the accepted sense of the word, and some of them have legitimate uses as well as being drugs of abuse. 

Uses.—It is necessary to distinguish clearly between the local and systemic effects of cocaine. When locally applied cocaine is a paralyzant to the peripheral ends of the sensory nerves, and to a lesser degree to the motor nerves, and stimulating to the muscular coats of the blood vessels. As a result of these actions when painted over mucous membranes it causes blanching of the part and diminished sensation. It produces not only lessened serisibility to pain and touch but also of the acuity of the special senses, thus it diminishes in the mouth the power of taste and in the nose that of smell. 

Many northern states, however, also had anticannabis laws as early as 1915. To the legislators of Maine, Vermont, Massachusetts, and New York, a narcotic was a narcotic, whatever its name. Cannabis was considered a narcotic and therefore was accorded the same status as opium, morphine, heroin, and codeine, all of which were proscribed. Thus, when New York City s Board of Health prohibited cannabis from the city s streets in 1914, the New York Times (July 30, 1914) reported that the drag was a "narcotic [with] practically the same effect as morphine and cocaine... [and] the inclusion of cannabis indica among the drags to be sold only on prescription is only common sense. Devotees of hashish are now hardly numerous here to count, but they are likely to increase as other narcotics become harder to obtain."... 

The coabuse of cocaine and alcohol is all too common (Grant and Harford 1990), and is thought to result from the enhanced euphoria and sense of well-being experienced when cocaine is taken with alcohol (Farre et al. 1993). Unfortunately, coabuse of alcohol and cocaine results in an increased health risk (Farre et al. 1993). The formation of cocaethylene under defined experimental conditions in rats after administration of alcohol and cocaine and the cellular and organ toxicity of cocaethylene are discussed by Dean and colleagues elsewhere in this volume. 

What Bob may not know yet is that cocaine is not an adequate replacement for the excitement and sense of accomplishment he misses in his life. It may help him recapture the feelings he had on the football field for a time, but eventually even those feelings will fade as his tolerance to cocaine increases. 

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