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

@article{Baumann2013PowerfulCA,
  title={Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products},
  author={Michael H Baumann and John S. Partilla and Kurt R. Lehner and Eric B. Thorndike and Alexander F. Hoffman and Marion Holy and Richard B. Rothman and Steven R. Goldberg and Carl R. Lupica and Harald H. Sitte and Simon D Brandt and Srihari R. Tella and Nicholas V Cozzi and Charles W Schindler},
  journal={Neuropsychopharmacology},
  year={2013},
  volume={38},
  pages={552-562}
}
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… 

Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats

TLDR
The hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs is supported.

3,4-Methylenedioxypyrovalerone: Neuropharmacological Impact of a Designer Stimulant of Abuse on Monoamine Transporters

TLDR
Pharmacological characterization of the synthetic cathinone, 3,4-methylenedioxypyrovalerone (MDPV; commonly referred to as a “bath salt”), is critical for understanding the abuse liability and neurotoxic potential of this and related agents and contributes to a growing pharmacological rubric for evaluating the ever-growing list of designer Cathinone-related stimulants.

Stereoselective Effects of Abused “Bath Salt” Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

TLDR
It is suggested that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse.

Stereoselective Actions of Methylenedioxypyrovalerone (MDPV) To Inhibit Dopamine and Norepinephrine Transporters and Facilitate Intracranial Self-Stimulation in Rats.

TLDR
The results indicate that abuse-related neurochemical and behavioral effects of racemic MDPV reside primarily with its S(+) isomer.

Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs.

TLDR
Findings in this chapter demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.

Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure

TLDR
A significant enhanced effect of MDPV, mephedrone, and methylone on both DA and DA metabolite levels is demonstrated, and these effects on DA result in significant alterations in locomotor activity.

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

TLDR
Observed locomotor stimulation was mediated by elevated DA-ergic neurotransmission, as all compounds caused a significant increase of extracellular DA levels in the striatum, with 3,4-MDPV being the most potent, and psychostimulant effects were abolished by SCH 23390.

The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats.

TLDR
Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats, and these data suggest that benzofuran-type compounds may have abuse liability and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.
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References

SHOWING 1-10 OF 57 REFERENCES

4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse

TLDR
Evaluated effects of the designer stimulant 4-methylmethcathinone in a rat model demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential.

The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue

TLDR
In vitro and in vivo methods demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA.

Evidence for the Involvement of Dopamine Transporters in Behavioral Stimulant Effects of Modafinil

TLDR
The data show that modafinil interacts with DAT sites in rat brain, a property shared with agonist medications under investigation for treating cocaine dependence, and suggest that modAFinil should be tested as an adjunct for treating METH addiction.

Methylone and Monoamine Transporters: Correlation with Toxicity

TLDR
The ability of methylone to inhibit monoamine transporter function, probably by acting as a transportable substrate, underlies the synergistic effect of methyl one and methamphetamine.

Interaction of mephedrone with dopamine and serotonin targets in rats

The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

TLDR
MDMA-induced 5- HT depletions are not necessarily synonymous with neurotoxic damage, however, doses of MDMA which do not cause long-term 5-HT depletion can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.

In Vivo Effects of Amphetamine Analogs Reveal Evidence for Serotonergic Inhibition of Mesolimbic Dopamine Transmission in the Rat

TLDR
The findings are consistent with the hypothesis that 5-HT release dampens stimulant effects of amphetamine-type drugs, but further studies are required to address the precise mechanisms underlying this phenomenon.

In Vitro Characterization of Ephedrine-Related Stereoisomers at Biogenic Amine Transporters and the Receptorome Reveals Selective Actions as Norepinephrine Transporter Substrates

TLDR
The data indicate that the pharmacological effects of ephedrine-like phenylpropanolamines are likely mediated by norepinephrine release, and although sharing mechanistic similarities with, they differ in important respects from those of the phenyl Propanonamines methcathinone and cathin one and the phenyisopropylamines methamphetamine and amphetamine.
...