A Controlled Evaluation of Pyrovalerone in Chronically Fatigued
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Goldberg, Jonathan; Gárdos, George; Jo, Cole

doi:10.1159/000467975

Cited by 33 publications

(26 citation statements)

References 9 publications

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“…Despite the widespread use of MDPV, no information is available regarding its molecular mechanism of action. Older literature demonstrates that pyrovalerone, a compound with structural similarity to MDPV, displays amphetamine-like stimulant properties in rodents (Fauquet et al, 1976;Vaugeois et al, 1993) and humans (Goldberg et al, 1973;Holliday et al, 1964). Bonnet and colleagues (Heron et al, 1994;Tidjane Corera et al, 2001) showed that pyrovalerone is a dopamine uptake blocker that interacts with transporter proteins in a manner similar to cocaine.…”

Section: Introductionmentioning

confidence: 99%

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Baumann

Partilla

Lehner

et al. 2012

Neuropsychopharmacol

374

453

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The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [ 3 H]dopamine (IC 50 ¼ 4.1 nM) and [ 3 H]norepinephrine (IC 50 ¼ 26 nM) with high potency but has weak effects on uptake of [ 3 H]serotonin (IC 50 ¼ 3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.

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Section: Introductionmentioning

confidence: 99%

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Baumann

Partilla

Lehner

et al. 2012

Neuropsychopharmacol

374

453

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“…Also known as "Cat" and "Jeff," it has been used recreationally most often in countries formerly part of the Soviet Union, but also gained popularity in the United States, particularly in Michigan, in the 1990s [7]. Another derivative, pyrovalerone was investigated for use as a prescription drug to treat chronic fatigue, lethargy, and obesity but was withdrawn due to abuse and dependency in users [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

2011

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Synthetic cathinones have recently emerged and grown to be popular drugs of abuse. Their dramatic increase has resulted in part from sensationalized media attention as well as widespread availability on the Internet. They are often considered "legal highs" and sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are derivatives of this compound. Those that are being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3-and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. Synthetic cathinones are phenylalkylamines derivatives, and are often termed "bk-amphetamines" for the beta-ketone moiety. They may possess both amphetaminelike properties and the ability to modulate serotonin, causing distinct psychoactive effects. Desired effects reported by users of synthetic cathinones include increased energy, empathy, openness, and increased libido. Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. Deaths associated with use of these compounds have been reported. Exposure to and use of synthetic cathinones are becoming increasingly popular despite a lack of scientific research and understanding of the potential harms of these substances. The clinical similarities to amphetamines and MDMA specifically are predictable based on the chemical structure of this class of agents. More work is necessary to understand the mechanisms of action, toxicokinetics, toxicodynamics, metabolism, clinical and psychological effects as well as the potential for addiction and withdrawal of these agents.

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“…Despite these indications that MDPV may be a growing public health concern, it remains the case that scant information is available regarding its mechanism of action or in vivo effects. In this regard, the structurally similar pyrovalerone has been shown to stimulate spontaneous locomotor activity in rodents (Fauquet et al, 1976;Vaugeois et al, 1993) and to induce stimulant-like actions in humans (Holliday et al, 1964;Goldberg et al, 1973). More recently, it was demonstrated that pyrovalerone has cocaine-like effects at dopamine reuptake transporters (Heron et al, 1994;Tidjane Corera et al, 2001;Meltzer et al, 2006) and that these effects are also apparent in MDPV itself (Baumann et al, 2012b;Simmler et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3 mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED 50 values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30 mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30 mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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A Controlled Evaluation of Pyrovalerone in Chronically Fatigued Volunteers

Cited by 33 publications

References 9 publications

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

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