how is cocaethylene formed

Is Cocaethylene an active metabolite?

Cocaethylene is an active metabolite responsible for life-threatening toxicity if cocaine and alcohol are abused simultaneously.

What is the LD50 of Cocaethylene?

The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.

How is benzoylecgonine produced?

Benzoylecgonine is the major metabolite of cocaine. It is formed by hydrolysis of cocaine in the liver, catalysed by carboxylesterases. It is excreted in the urine of cocaine users after processing in the liver.

What is Norcocaine used for?

The local anesthetic potential of norcocaine has been shown to be higher than that of cocaine, however cocaine continues to be more widely used. Norcocaine used for research purposes is typically synthesized from cocaine....Norcocaine.Clinical dataCAS Number18717-72-1PubChem CID644007ChemSpider559083UNII3SL7BR2M1E13 more rows

What is the meaning of Cocaethylene?

Cocaethylene (ethylbenzoylecgonine) is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed by the liver when cocaine and ethanol coexist in the blood.

How long does it take for alcohol to get out of your system?

The half-life of alcohol is four to five hours. A half-life is how long it takes for your body to get rid of half of it. But you need about five half-lives to get rid of alcohol completely. So, it takes about 25 hours for your body to clear all the alcohol.

What else is benzoylecgonine found in?

Benzoylecgonine is sometimes found in drinking water supplies. In 2005, scientists found surprisingly large quantities of benzoylecgonine in Italy's Po River and used its concentration to estimate the number of cocaine users in the region.

What can show up as benzoylecgonine?

CocaineCocaine is detected in urine by identification of benzoylecgonine, an inactive metabolite of cocaine.

How do I dispute a false positive drug test?

How Can I Dispute a False Positive Drug Test?Step 1: Get out in front of the issue. ... Step 2: Ask your doctor or pharmacist. ... Step 3: Ask to retake the drug test.

What is levamisole used for?

Levamisole is an immunomodulatory agent that was used to treat various cancers before being withdrawn from the United States market in 2000 because of adverse effects. Levamisole is currently approved as an antihelminthic agent in veterinary medicine, but is also being used illicitly as a cocaine adulterant.

What is a metabolite in a drug test?

A metabolite forms when a substance breaks down into the body. Basically, it means that the parent drug has been turned into something else. Because THC metabolites remain in the body much longer than THC itself, drug tests for cannabis are used to detect THC metabolites.

What is benzoylecgonine and ecgonine methyl ester?

Benzoylecgonine (BE) and ecgonine methyl ester (EME) are supposed to be the major hydrolysis products in human plasma. BE is formed by chemical hydrolysis of the methyl ester group, and small amounts of EME are formed enzymati- cally by hydrolysis of the benzoyl ester (2,4).

What is benzoylecgonine and ecgonine methyl ester?

Benzoylecgonine (BE) and ecgonine methyl ester (EME) are supposed to be the major hydrolysis products in human plasma. BE is formed by chemical hydrolysis of the methyl ester group, and small amounts of EME are formed enzymati- cally by hydrolysis of the benzoyl ester (2,4).

What is levamisole used for?

Levamisole is an immunomodulatory agent that was used to treat various cancers before being withdrawn from the United States market in 2000 because of adverse effects. Levamisole is currently approved as an antihelminthic agent in veterinary medicine, but is also being used illicitly as a cocaine adulterant.

How is cocaethylene formed?

Cocaethylene is formed by the liver when cocaine and ethanol coexist in the blood . In 1885, cocaethylene was first synthesized (according to edition 13 of the Merck Index ), and in 1979, cocaethylene's side effects were discovered.

What is the chemical name for Cocaethylene?

Cocaethylene. Cocaethylene ( ethylbenzoylecgonine) is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine . Cocaethylene is formed by the liver when cocaine and ethanol coexist in the blood.

What is the metabolic process of cocaine?

Metabolic production from cocaine. Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. Normally, metabolism of cocaine produces two primarily biologically inactive metabolites — benzoylecgonine and ecgonine methyl ester.

Does coke increase dopamine?

Cocaethylene increases the levels of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain by inhibiting the action of the serotonin transporter, norepinephrine transporter, and dopamine transporter.

Is cocaethylene a recreational drug?

Cocaethy lene is largely considered a recreational drug in and of itself, with stimulant, euphoriant, anorectic, sympathomimetic, and local anesthetic properties. The monoamine neurotransmitters serotonin, norepinephrine, and dopamine play important roles in cocaethylene's action in the brain.

Is cocaethylene a serotonin?

These pharmacological properties make cocaethylene a serotonin-norepinephrine- dopamine reuptake inhibitor (SNDRI; also known as a "triple reuptake inhibitor"). In most users, cocaethylene produces euphoria and has a longer duration of action than cocaine.

What is the active metabolite of cocaine?

Cocaethylene, also known as ethylbenzoylecgonine, is an active metabolite of cocaine formed in the liver when the illicit drug cocaine is consumed along with alcohol.

How does alcohol interact with cocaine?

However, if both of these substances are present, alcohol can interact with cocaine as it’s metabolized through a process called transesterification. This creates cocaethylene.

Does alcohol increase cocaethylene?

However, the heightened intoxication interferes with coordination, focus, judgment, and inhibition, increasing the likelihood that an individual will continue binging alcohol in the short-term and further increase cocaethylene formation.

Does cocaethylene increase dopamine?

Cocaethylene increases dopamine activity in the brain by interfering with dopamine transporter proteins and dopamine reuptake, meaning that the presence of cocaethylene can increase intoxication and euphoria when compared to use of alcohol or cocaine alone.

Is cocaethylene toxicity higher than cocaine?

Research suggests that cocaethylene toxicity may be more than 30% higher than cocaine alone . The drug also has a longer half-life than cocaine, meaning that once it is present in the body it can last up to three times longer.

Can cocaine cause miscarriage?

Combining cocaine and alcohol during pregnancy can result in miscarriage, stillbirth, premature birth, low birth weight, and developmental issues. Developmental issues are also possible if alcohol and cocaine are used prior to breastfeeding.

Does cocaine cause heart attacks?

Cocaethylene has an even more severe impact on cardiovascular function than cocaine, with its most serious effects impacting heart muscle contraction, heart rate, and blood pressure. These effects greatly increase the risk of heart attack, even after the first use.

What is cocaethylene?

Soon after the extraction and purification of cocaine, its local anesthetic and stimulant properties were discovered and this natural product became a major recreational drug of abuse worldwide ( 11 ).

What is the metabolite of cocaine?

The principal metabolites of cocaine of most interest in forensic toxicology are benzoylecgonine (BZE) and ecgonine methyl ester (EME), which are determined in blood ( 15) and excreted in urine, BZE being the target analyte for screening analysis ( 16 ).

What is the chemical that is found in the body when you ingest ethanol?

This article is intended as a brief review or primer about cocaethylene (CE), a pharmacologically active substance formed in the body when a person co-ingests ethanol and cocaine. Reference books widely used in forensic toxicology contain scant information about CE, even though this cocaine metabolite is commonly encountered in routine casework. CE and cocaine are equi-effective at blocking the reuptake of dopamine at receptor sites, thus reinforcing the stimulant effects of the neurotransmitter. In some animal species, the LD50 of CE was lower than for cocaine. CE is also considered more toxic to the heart and liver compared with the parent drug cocaine. The plasma elimination half-life of CE is ~2 h compared with ~1 h for cocaine. The concentrations of CE in blood after drinking alcohol and taking cocaine are difficult to predict and will depend on the timing of administration and the amounts of the two precursor drugs ingested. After an acute single dose of cocaine and ethanol, the concentration–time profile of CE runs on a lower level to that of cocaine, although CE is detectable in blood for several hours longer. A strong case can be made for adding together the concentrations of cocaine and CE in forensic blood samples when toxicological results are interpreted in relation to acute intoxication and the risk of an overdose death.

How is CE formed?

The same investigators from Miami showed that CE was rapidly formed when liver homogenates were incubated with ethanol and cocaine ( 20 ). This line of research was extended by Jatlow et al. ( 24 ), who confirmed that CE was not an artifact produced during the work-up of specimens. To drug-free blood they added both ethanol and cocaine and no CE was formed when the mixture was incubated 37°C. Neither was CE produced when the incubation mixture were acidified (pH 1–2) to simulate conditions existing in the stomach.

How are cocaine and CE similar?

The close similarity in chemical structure and physicochemical properties of cocaine and CE (see Figure 1) means that the two drugs are co-extracted from biological media, either by shaking with organic solvents or the use of solid-phase extraction columns ( 28 ). Both drugs have been identified and quantified in a wide variety of biological specimen types, including blood, oral fluid, meconium, plasma, urine and hair strands ( 29 ).

What enzymes are involved in the formation of cocaine?

Another minor and pharmacologically active metabolite of cocaine is formed by the action of hepatic P450 enzymes causing N -demethylation of the tertiary amine group to give norcocaine ( 6 ). A targeted analysis of CE should be considered whenever forensic blood samples are positive for both cocaine and ethanol.

Does cocaine cause relapse?

Cocaine exerts powerfully reinforcing effects after chronic use, which leads to physiological and psychological dependence. Many people exhibit drug-seeking behavior and accordingly they tend to relapse after a period of abstinence ( 43 ). There is no effective pharmacotherapy for treatment of cocaine addiction, although this is an active and ongoing area of research ( 48 ).

Where is cokeethylene produced?

Studies have also shown that Cocaethylene is only produced within the liver when alcohol is consumed 'before' administration of cocaine. [3]

What is cocaine metabolite?

They discovered that: "When cocaine is consumed in the absence of alcohol, it is broken down into two principle metabolites: one called benzoylecgonine and one called ecgonine methyl ester. In humans, at least, neither of the two had any stimulant or psychological effects, but cocaethylene does, nearly as much stimulation as cocaine. When the two are consumed together cocaine's stimulating effects are enhanced and prolonged. Vin Mariani's drinkers were, in effect, getting more cocaine than either Mariani or his competitors thought they were providing." [6]

How much cocaine is transesterified?

About 1/6th of the cocaine administered undergoes transesterification and is changed into cocaethylene in the body when taken with alcohol. [2] As much as 24% when cocaine is taken by intravenous route of administration.

What is the compound that is produced when alcohol is mixed with cocaine?

They discovered, in 1990, that when alcohol was mixed with cocaine the liver actually produced a third compound called Cocaethylene. [1]

Is cocaethylene toxic?

Most of the research undertaken has had some alarming results - cocaethylene, although making its consumer highly euphoric and much more stimulated, was much more deadly and toxic than cocaine use alone.

Is cocaine more cardiotoxic than alcohol?

Concurrent use of cocaine and alcohol has been associated with greater risk of sudden death than after cocaine alone. [5] Cocaethylene is more cardiotoxic than cocaine itself, causing more stress on the cardiovascular system.

Is cocaethylene a metabolite?

An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite. Cocaethylene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol.

Is cocaethylene a natural alkaloid?

Not a natural alkaloid of the coca leaf, cocaethylene can be identified in the urine, blood, hair, and neurological and liver tissue samples of individuals who hav …. Cocaethy lene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol. Not a natural alkaloid of the coca leaf, ...

Is cocaethylene more euphoric than cocaine?

Lacking the serotonergic-related inhibitory mechanism, cocaethylene appears to be more euphorigenic and rewarding than coca ine.

Does cocaine block dopamine?

With a pharmacologic profile similar to cocaine, it can block the dopamine transporter on dop aminergic presynaptic nerve terminals in the brain. It increases dopamine synaptic content, provoking enhanced postsynaptic receptor stimulation, resulting in euphoria, reinforcement, and self-administration.

Is cocaethylene a psychoactive substance?

Cocaethylene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol. Not a natural alkaloid of the coca leaf, cocaethylene can be identified in the urine, blood, hair, and neurological and liver tissue samples of individuals who have consumed both cocaine and alcohol.

Is cocaethylene a substitute for cocaine?

Equipotent to cocaine with regard to primate reinforcement and self-administration, cocaethylene can substitute for cocaine in drug discrimination studies, and can produce stimulation of operant conditioning in rats. With regard to lethality, cocaethylene has been shown to be more potent than cocaine in mice and rats.

What is the metabolic process of cocaine?from en.wikipedia.org

Metabolic production from cocaine. Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. Normally, metabolism of cocaine produces two primarily biologically inactive metabolites — benzoylecgonine and ecgonine methyl ester.

Where is C. formed?from quizlet.com

C. is formed in the body when cocaine and alcohol are used together.

Is Cocaethylene a freebase drug?from quizlet.com

is formed in the body when cocaine and alcohol are used together. Cocaethylene. is a type of freebase cocaine that uses ether. was one of the popular patent medicines sold around 1900. is formed in the body when cocaine and alcohol are used together.

Is cocaethylene a serotonin?from en.wikipedia.org

These pharmacological properties make cocaethylene a serotonin-norepinephrine- dopamine reuptake inhibitor (SNDRI; also known as a "triple reuptake inhibitor"). In most users, cocaethylene produces euphoria and has a longer duration of action than cocaine.

Introduction

What Is Cocaethylene?

Discovery of Cocaethylene

Analytical Methods

Pharmacokinetics

Pharmacodynamics

• Cocaine was extracted from Erythroxylum coca in 1860 (8) by Albert Niemann (1834–1861) and its chemical structure was elucidated by Richard Willstätter (1872–1942) as part of his doctoral thesis on tropane alkaloids done at the University of Munich in 1894 (9, 10). According to the MERCK index (13th edition) cocaethylene was first prepared in 1885,...

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Blood Concentrations of CE

Toxicity

Concluding Remarks