Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products.
Citations
313 citations
Cites background from "Powerful cocaine-like actions of 3,..."
...…when applied to synaptosomes, not only block DAT and SERT uptake (Baumann et al., 2012a, Martinez-Clemente et al., 2012) but act as DAT and SERT substrates, releasing neurotransmitter from synaptosomes (Baumann, Ayestas, 2012a, Baumann et al., 2012b, Cameron et al., 2012, Hadlock, Webb, 2011)....
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...In vitro transporter assays further confirm that mephedrone and methylone, when applied to synaptosomes, not only block DAT and SERT uptake (Baumann et al., 2012a, Martinez-Clemente et al., 2012) but act as DAT and SERT substrates, releasing neurotransmitter from synaptosomes (Baumann, Ayestas,…...
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278 citations
Cites background from "Powerful cocaine-like actions of 3,..."
...Despite the scarcity of experimental data on the pharmacological and toxicological properties of these ‘legal highs’, based on the structural similarities of cathinone derivatives with other amphetamines like MDMA (3,4-methylenedioxymethamphetamine, ‘ecstasy’), identical effects are predictable....
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...MDPv acts as a pure monoamine-selective transporter blocker, with high potency for DAT and NeT (50-fold and 10-fold more potent than cocaine, respectively), but weak for SeRT (10- fold less potent than cocaine) (Baumann et al. 2013b; cameron et al. 2013)....
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...Phase II metabolic pathways may include reactions of acetylation, glucuronidation or sulfonation of the hydroxyl groups, with the resultant metabolites being excreted in the urine. like amphetamine, MeTH, and MDMA, synthetic cathinones exert their effects by interacting with catecholamine transporters (DAT, NeT, and SeRT), which results in increased synaptic concentrations of these monoamines....
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...Nonetheless, MePH was shown to potentiate the neurotoxicity evoked by other illicit drugs, such as MeTH, amphetamine, and MDMA (Angoa-Pérez et al. 2013)....
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...On one hand, MePH is capable of inducing MDMA- and cocainelike subjective effects, which may contribute to its indiscriminate abuse (carhart-Harris et al. 2011; Deluca et al. 2009b)....
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217 citations
Cites background from "Powerful cocaine-like actions of 3,..."
...potentiates release, while a blocker is inactive (for an example see the characterization of MDPV in [84]....
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202 citations
Cites background from "Powerful cocaine-like actions of 3,..."
...MDPV is at least 10 times more potent than cocaine at producing locomotor activation and stereotypies [41], while mephedrone-induced effects on locomotor activity are similar to MDMA but lower than amphetamine [42]....
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...MDPV-related psychoactive effects resembling those of cocaine, which lasts from 3 to 4 hours [41]....
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188 citations
Cites background from "Powerful cocaine-like actions of 3,..."
...Uptake inhibitors differ from releasers only in appearing to tolerate a greater proportion of 5HT effects than releasers (c.f. MDMA and cocaine are relatively nonselective compounds at DAT versus SERT, but cocaine produces more robust ICSS facilitation)....
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...MK801 has not been approved for clinical use and has not been considered for scheduling by the FDA, but for the remaining three compounds, the hierarchy of abuse potential from ICSS studies corresponds roughly to the FDA scheduling hierarchy for these compounds, where PCP is schedule 1, ketamine is schedule 3, and memantine is unscheduled....
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...Effects of repeated/ chronic treatment with monoamine uptake inhibitors have been evaluated with cocaine and with some SERT- and NET-selective uptake inhibitors that are used clinically as antidepressants....
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...Methylenedioxypyrovalerone (MDPV) is a cathinone derivative that has recently emerged as a designer drug of abuse often included in “bath salts,” and it has been designated as a schedule 1 drug by the U.S. Food and Drug Administration (FDA) (Baumann et al., 2013b)....
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...Of particular relevance to abuse potential testing, a family of novel monoamine releasers (and uptake inhibitors, see below) with street names such as “bath salts” has recently emerged as a new source of illicit drugs in Europe and North America (Baumann et al., 2013a; De Felice et al., 2014)....
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References
884 citations
"Powerful cocaine-like actions of 3,..." refers background or methods in this paper
...In Vitro Uptake and Release Assays in Synaptosomes Rats were euthanized by CO2 narcosis, and the brains were processed to yield synaptosomes as previously described (Rothman et al, 2001; Rothman et al, 2003b)....
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...It is well established that traditional uptake inhibition assays cannot distinguish between drugs acting as transporter blockers vs those acting as substrates (ie, releasers; Rothman et al, 2001; Rothman et al, 2003b)....
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...For example, we have shown that established uptake blockers like GBR12909 and indatraline display low-efficacy releasing effects in synaptosomes (Rothman and Baumann, 2003a; Rothman et al, 2001)....
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810 citations
"Powerful cocaine-like actions of 3,..." refers background in this paper
...It is well established that drug-induced elevations in extracellular dopamine in the nucleus accumbens are involved with locomotor-activating properties of stimulant drugs (Ikemoto, 2002; Pennartz et al, 1994)....
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680 citations
"Powerful cocaine-like actions of 3,..." refers background in this paper
...…but not blockers, are known to produce long-term deficits in monoamine neurons that are often viewed as neurotoxicity (Baumann et al, 2007; Fleckenstein et al, 2007); and (3) Neuropsychopharmacology there are conflicting reports in the literature regarding the precise interactions of…...
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591 citations
"Powerful cocaine-like actions of 3,..." refers methods in this paper
...In the superfusion experiments, cells are pretreated with the Naþ /Hþ ionophore monensin, which alters ionic gradients to increase cytoplasmic Naþ (Mollenhauer et al, 1990; Turetta et al, 2004)....
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499 citations
"Powerful cocaine-like actions of 3,..." refers background in this paper
...All rights reserved 0893-133X/12 www.neuropsychopharmacology.org Holstege, 2012; Kyle et al, 2011; Murray et al, 2012; Spiller et al, 2011)....
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...All three of the Schedule I cathinones, depicted in (Figure 1), have been identified in bath salts products (Ross et al, 2011; Spiller et al, 2011), but MDPV is the chief substance found in the blood and urine from patients exposed to bath salts who are admitted to emergency departments in the…...
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...…(eg, caffeine) can be found in bath salts products, but MDPV is the main compound detected in biological fluids from patients admitted to emergency departments for bath salts overdose in the United States (Borek and Holstege, 2012; Kyle et al, 2011; Murray et al, 2012; Spiller et al, 2011)....
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...In particular, synthetic analogs of the plantderived stimulant cathinone are being sold online and in retail shops as legal alternatives to illicit drugs like cocaine, amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA; Ross et al, 2011; Spiller et al, 2011)....
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...…to emergency departments for bath salts overdose, who have toxicological verification of MDPV consumption, display symptoms, including agitation, psychosis, violent behavior, hyperthermia, and tachycardia (Borek and Holstege, 2012; Kyle et al, 2011; Murray et al, 2012; Spiller et al, 2011)....
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