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Emerging drugs of abuse: current perspectives on substituted cathinones.

Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D - Subst Abuse Rehabil (2014)

Bottom Line: They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects.Desired effects reported by users include increased energy, empathy, and improved libido.Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.

View Article: PubMed Central - PubMed

Affiliation: Toxicology and Pharmacology Laboratory, University Hospital Centre, Caen, France.

ABSTRACT
Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of synthetic cathinones.
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f1-sar-5-037: Chemical structure of synthetic cathinones.

Mentions: Substituted cathinones are a large family of synthetic beta-keto phenethylamine (2-amino-1-phenyl-1-propanone) derivatives chemically related to the parent compound cathinone, a monoamine alkaloid naturally present in the khat plant, differing only in the functionality present at the beta-carbon; ie, ketone oxygen. As with amphetamines, both systematic (International Union of Pure and Applied Chemistry) and non-standard nomenclature is common in cathinone chemistry. The use of acronyms is also widespread. As a consequence of the beta-keto substituent, it is also common practice for widely accepted amphetamine acronyms to be augmented with the prefix “bk”. The most common cathinones and their related trade names are listed in Table 1. The general structure of a cathinone derivative (Figure 1) shows substitution patterns at four locations of the cathinone molecule; eg, on the carbon atom linked to the carbon in alpha position (R1), on the nitrogen atom (R2 and R3), and on the phenyl group (R4). Substituents in R1, R2, R3, and R4 may vary, and include: alkyl, alkoxy, alkylenedioxy, haloalkyl, halide, and phenyl. However, differences between substituted cathinones may be limited to the simple addition of a methyl group (Table 2). For some substituted cathinones, nitrogen may be incorporated in a cyclic pyridinyl structure leading to the series of compounds presented in Table 3. Some others are methylenedioxy-substituted analogs differing from their corresponding methylenedioxy amphetamines by the addition of only a beta-ketone group (Table 4). Moreover, besides substituted 2-amino-1-phenyl-1-propanones, some 1-amino-1-phenyl-2-propanone derivatives are now emerging, including isoethcathinone and isopentedrone. All these compounds are chiral, and can exist in two stereoisomer forms. Aside from their usual trade names, substituted cathinones may be intentionally mislabeled and retailed under slang names as bath salts, plant food, or research chemicals and be labeled not for human consumption. They may be referred to by specific street names, such as meow-meow, MCAT, meph, subcoca-1, and so on, for mephedrone or by generic brand names as Energy 1, 2, or 3 (NRG1, 2, or 3), Blizzard, Blue silk, and Ivory snow among others. Qualitative analyses have been carried out on so called legal highs or NRG that have been obtained from different websites. They showed that: 1) the real composition of many of the products were found to differ markedly from information given to the purchaser, and 2) the majority of these products contained a mixture of substituted cathinones,1 which increased poisoning risk.


Emerging drugs of abuse: current perspectives on substituted cathinones.

Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D - Subst Abuse Rehabil (2014)

Chemical structure of synthetic cathinones.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043811&req=5

f1-sar-5-037: Chemical structure of synthetic cathinones.
Mentions: Substituted cathinones are a large family of synthetic beta-keto phenethylamine (2-amino-1-phenyl-1-propanone) derivatives chemically related to the parent compound cathinone, a monoamine alkaloid naturally present in the khat plant, differing only in the functionality present at the beta-carbon; ie, ketone oxygen. As with amphetamines, both systematic (International Union of Pure and Applied Chemistry) and non-standard nomenclature is common in cathinone chemistry. The use of acronyms is also widespread. As a consequence of the beta-keto substituent, it is also common practice for widely accepted amphetamine acronyms to be augmented with the prefix “bk”. The most common cathinones and their related trade names are listed in Table 1. The general structure of a cathinone derivative (Figure 1) shows substitution patterns at four locations of the cathinone molecule; eg, on the carbon atom linked to the carbon in alpha position (R1), on the nitrogen atom (R2 and R3), and on the phenyl group (R4). Substituents in R1, R2, R3, and R4 may vary, and include: alkyl, alkoxy, alkylenedioxy, haloalkyl, halide, and phenyl. However, differences between substituted cathinones may be limited to the simple addition of a methyl group (Table 2). For some substituted cathinones, nitrogen may be incorporated in a cyclic pyridinyl structure leading to the series of compounds presented in Table 3. Some others are methylenedioxy-substituted analogs differing from their corresponding methylenedioxy amphetamines by the addition of only a beta-ketone group (Table 4). Moreover, besides substituted 2-amino-1-phenyl-1-propanones, some 1-amino-1-phenyl-2-propanone derivatives are now emerging, including isoethcathinone and isopentedrone. All these compounds are chiral, and can exist in two stereoisomer forms. Aside from their usual trade names, substituted cathinones may be intentionally mislabeled and retailed under slang names as bath salts, plant food, or research chemicals and be labeled not for human consumption. They may be referred to by specific street names, such as meow-meow, MCAT, meph, subcoca-1, and so on, for mephedrone or by generic brand names as Energy 1, 2, or 3 (NRG1, 2, or 3), Blizzard, Blue silk, and Ivory snow among others. Qualitative analyses have been carried out on so called legal highs or NRG that have been obtained from different websites. They showed that: 1) the real composition of many of the products were found to differ markedly from information given to the purchaser, and 2) the majority of these products contained a mixture of substituted cathinones,1 which increased poisoning risk.

Bottom Line: They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects.Desired effects reported by users include increased energy, empathy, and improved libido.Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.

View Article: PubMed Central - PubMed

Affiliation: Toxicology and Pharmacology Laboratory, University Hospital Centre, Caen, France.

ABSTRACT
Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.

No MeSH data available.


Related in: MedlinePlus