Synthetic cathinones like MDPV emerged as drugs of abuse in the early 2010s, gaining notoriety for their powerful stimulant effects and association with bizarre intoxication and death.
Despite legislation banning MDPV and its analogs, these substances continue circulating in the drug marketplace.
Understanding the pharmacology of MDPV provides insight on its abuse liability, toxic effects, detection, and potential treatment approaches.
Key Facts:
- MDPV is a potent blocker of dopamine and norepinephrine transporters, increasing signaling by these neurotransmitters.
- The S-isomer of MDPV is responsible for most of its pharmacological activity.
- MDPV elevates extracellular dopamine but not serotonin, distinguishing it from other synthetic cathinones.
- MDPV is rapidly absorbed and metabolized after administration. The parent compound correlates with behavioral effects.
- Replacement analogs like α-PVP maintain abuse liability by similar transporter actions.
Source: Curr Top Behav Neurosci.
Powerful Neurochemical Effects of MDPV
MDPV belongs to a class of drugs called synthetic cathinones which are chemically similar to cathinone, the psychoactive component of the khat plant.
MDPV contains a pyrrolidine ring structure that enables it to potently block the reuptake transporters for dopamine and norepinephrine in the brain.
This inhibition of reuptake leads to accumulation of dopamine and norepinephrine in synaptic regions, amplifying signaling by these catecholamine neurotransmitters.
In contrast, other synthetic cathinones like mephedrone and methylone act as transporter substrates, not just inhibitors, meaning they are transported into nerve cells to trigger reverse transport and release of transmitters.
MDPV is too bulky to fit inside transporters, so it can only bind and inhibit them.
Experiments in rats showed MDPV increases extracellular dopamine in reward centers like the nucleus accumbens, but does not affect serotonin.
This likely explains its powerful locomotor stimulant and reinforcing properties mediated by dopamine.
Stereoisomers and Metabolism of MDPV
MDPV exists as a racemic mixture of R and S stereoisomers.
Studies found the S form is 50-100 times more potent than the R form at inhibiting dopamine and norepinephrine transporters and producing behavioral effects.
This indicates the psychoactive properties of MDPV reside predominantly in the S isomer.
MDPV is rapidly absorbed into the bloodstream upon administration.
It undergoes metabolism in the liver to compounds like 3,4-catechol-PV and 4-OH-3-MeO-PV.
In rats, MDPV itself correlates with stimulant effects, whereas metabolites do not, suggesting the parent compound is mainly responsible for pharmacological actions.
However, metabolites may serve as markers of MDPV exposure for forensic detection purposes.
Replacement MDPV Analogs Maintain Abuse Potential
After MDPV was banned, replacement analogs appeared like α-PVP.
Despite lacking the methylenedioxy ring, α-PVP retains potent blockade of dopamine and norepinephrine transporters.
Experiments found α-PVP increases extracellular dopamine and stimulates locomotor activity in rats like MDPV.
It also exhibits similar self-administration in rats, indicating high abuse potential.
Other analogs maintain transporter actions as well.
Implications and Unknowns
The pharmacology studies reviewed demonstrate MDPV and its analogs represent a distinct class of monoamine transporter inhibitors with powerful abuse liability.
However, questions remain regarding effects mediated specifically by norepinephrine, consequences of chronic use, and whether certain analogs could have therapeutic value for conditions involving dopamine deficiencies.
Understanding the precise mechanisms governing the behavioral actions of MDPV-like drugs will be essential for developing interventions and treatments.
Takeaways: MDPV Mechanisms of Action
In summary, this review of the literature on MDPV pharmacology reveals it is a highly potent inhibitor of dopamine and norepinephrine reuptake transporters, leading to accumulation of these neurotransmitters and amplification of their signaling.
In contrast to other synthetic cathinones, MDPV does not affect serotonin and its S-isomer is responsible for most pharmacological activity.
Upon administration, MDPV itself correlates with stimulant effects, whereas its metabolites appear inactive.
Despite the banning of MDPV, replacement analogs maintain abuse liability through similar transporter actions.
While much has been learned about the pharmacology of MDPV and related synthetic cathinones, important questions remain regarding mechanisms of action and therapeutic potentials that warrant further research.
References
- Study: Neuropharmacology of 3,4-methylenedioxypyrovalerone (MDPV), its metabolites, and related analogs
- Authors: Michael H. Baumann et al. (2017)
