generation run 2026-04-25
60 min completedmodel pipeline-v5plan not recordedrun/08fc0615…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
Reproduce
- inputs
- 36 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
25 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | MDPV dopamine transporter inhibitor DAT binding | 9 | 4 | All directly study MDPV at DAT or compare MDPV to cocaine at transporter level |
| 2 | OpenAlex | MDPV methylenedioxypyrovalerone synthetic cathinone | 10 | 6 | All highly cited and directly relevant to MDPV pharmacology or toxicology |
| 3 | PubMed | PMID 23072836 | 1 | 1 | Landmark paper on MDPV pharmacology |
| 4 | PubMed | MDPV 3,4-methylenedioxypyrovalerone pharmacology | 15 | 1 | Only article directly studying MDPV; others were general cathinone or unrelated papers |
| 5 | PubMed | methylenedioxypyrovalerone self-administration abuse liability rat | 10 | 2 | Directly relevant to MDPV reinforcing effects and abuse liability |
| 6 | PubMed | PMID 22387085 | 1 | 1 | Key case report on MDPV clinical toxicity |
| 7 | PubMed | PMID 22271565 | 1 | 1 | First reported fatality case report |
| 8 | PubMed | MDPV bath salts toxicology case report overdose | 2 | 2 | Both relevant as MDPV clinical reports |
| 9 | PubChem | MDPV | 1 | 1 | Only result, confirmed chemical identity data |
| 10 | WebSearch | MDPV bath salts Australia Schedule 9 prohibited substance scheduling | 10 | 1 | Australian legal scheduling |
| 11 | ClinicalTrials.gov · absence | MDPV methylenedioxypyrovalerone | 0 | — | No trials registered |
| 12 | WebSearch | MDPV 3,4-methylenedioxypyrovalerone history synthesis Boehringer Ingelheim patent 1969 | 10 | 2 | Confirms synthesis history and initial patent |
| 13 | Frontiers | MDPV pharmacokinetics behavior rats | 1 | 1 | Most comprehensive MDPV pharmacokinetic/behavioral profile in rats |
| 14 | PubMed | MDPV bath salts fatality blood concentration postmortem forensic | 5 | 4 | Forensic concentration data and fatality cases |
| 15 | WebSearch | MDPV legal status DEA Schedule I scheduling history US UK EU | 10 | 3 | Scheduling timeline for major jurisdictions |
| 16 | PubMed | MDPV bath salts intoxication psychosis agitation emergency department clinical presentation | 1 | 1 | Key clinical overview paper |
| 17 | PubMed · absence | MDPV cathinone tramadol serotonin toxicity death interaction | 0 | — | No direct evidence for tramadol-MDPV interaction in literature; seed data interaction not confirmed by published sources |
| 18 | WebSearch | MDPV methylenedioxypyrovalerone pharmacokinetics metabolism human CYP enzymes half-life | 10 | 5 | Core PK/metabolism papers |
| 19 | PMC | MDPV neuropharmacology metabolites | 1 | 1 | Critical stereochemistry and metabolite pharmacology data |
| 20 | PubMed | MDPV nucleus accumbens dopamine tachycardia cardiovascular sympathomimetic mechanism | 2 | 1 | Unique case documenting unusual sensory effects from MDPV |
| 21 | WebSearch/DEA/Wikipedia | MDPV CAS number physical properties SMILES | 5 | 2 | Fills chemical identity gaps not returned by PubChem API tool |
| 22 | PubMed | MDPV bath salts intoxication psychosis agitation emergency department clinical presentation | 1 | 1 | Most comprehensive single-source clinical MDPV overview |
| 23 | PubMed | MDPV bath salts fatality postmortem tissue distribution forensic | 5 | 4 | Key forensic concentration data and fatality documentation |
| 24 | PubMed | Aarde MDPV binge self-administration 2015 | 1 | 1 | MDPV binge self-administration characterization |
| 25 | OpenAlex | MDPV self-administration intravenous reinforcing rats cathinone | 8 | 2 | Key self-administration paper and public health review |
136 claims by section — every cited sentence, checked against its source
safety63 · 50 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Tachycardia: 63% of emergency presentationssupported
tachycardia 63% pmid:21597456
Agitation/aggression: predominant presenting complaint across seriessupported
Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, violent behavior. j.amjmed.2012.02.019
Hypertension: 25% of casessupported
hypertension (25.2%) s13181-012-0243-1
Hyperthermia: documented in multiple case reports; exacerbated by physical exertion and elevated ambient temperaturesupported
severe agitation, hyperthermia, tachycardia j.annemergmed.2012.01.005
Hyperthermia: documented in multiple case reports; exacerbated by physical exertion and elevated ambient temperaturesupported
Moderate hyperthermia exacerbated in group-housed animals. fpsyt.2018.00144
Diaphoresis and tachypneasupported
Physical: tachycardia, hypertension, arrhythmias, hyperthermia, sweating j.amjmed.2012.02.019
Rhabdomyolysis — documented in both oral and IV casessupported
rhabdomyolysis, cardiac injury, hepatic injury, renal failure j.annemergmed.2012.01.005
Rhabdomyolysis — documented in both oral and IV casessupported
CK 4,457 IU/dL pmid:24356039
Acute kidney injury — secondary to vasoconstriction, rhabdomyolysis, hyperthermia, and volume depletionsupported
rhabdomyolysis, cardiac injury, hepatic injury, renal failure j.annemergmed.2012.01.005
Acute kidney injury — secondary to vasoconstriction, rhabdomyolysis, hyperthermia, and volume depletionsupported
acute kidney injury (creatinine 15.2 mg/dL) pmid:24356039
Hepatic injury and multiorgan failuresupported
rhabdomyolysis, cardiac injury, hepatic injury, renal failure j.annemergmed.2012.01.005
Seizures, stroke, and cerebral edemasupported
rhabdomyolysis, seizures, stroke, cerebral edema, MI, death j.amjmed.2012.02.019
Myocardial infarction and cardiorespiratory collapsesupported
seizures, stroke, cerebral edema, MI, death j.amjmed.2012.02.019
Excited delirium syndrome — a state of extreme agitation, hyperthermia, and autonomic instability with significant mortality risksupported
Physical: tachycardia, hypertension, arrhythmias, hyperthermia... Behavioral: panic, anxiety, agitation... death. j.amjmed.2012.02.019
Excited delirium syndrome — a state of extreme agitation, hyperthermia, and autonomic instability with significant mortality risksupported
Excited delirium syndrome. First published case of idiosyncratic MDPV reaction. s12024-017-9894-1
Intravenous administration is associated with the most severe presentations, including multiorgan failure and acute kidney injury with choreoathetoid movements and gustatory/olfactory hallucinations.supported
25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure. j.annemergmed.2012.01.005
Intravenous administration is associated with the most severe presentations, including multiorgan failure and acute kidney injury with choreoathetoid movements and gustatory/olfactory hallucinations.supported
IV MDPV bath salts: sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, acute kidney injury (creatinine 15.2 mg/dL). pmid:24356039
Confirmation requires GC-MS or LC-MS/MS.supported
Not detected by routine drug screens. j.amjmed.2012.02.019
Confirmation requires GC-MS or LC-MS/MS.supported
Not detected on standard screens. pmid:24356039
Murray et al. (2012) reported the first documented MDPV death in the United States.supported
First reported death from MDPV use. s13181-011-0196-9
Wyman et al. (2013) established that blood MDPV concentrations ≥0.4 μg/mL (400 ng/mL) are sufficient to cause death via cardiac arrhythmia, with uniform tissue distribution at 0.4–0.6 μg/mL and higher concentrations (>0.8 μg/mL) in detoxification organs.supported
Postmortem MDPV distribution in tissues 0.4-0.6 μg/mL uniformly; detoxification organs (kidney, liver, bile) > 0.8 μg/mL. Blood concentration ≥0.4 μg/mL judged sufficient to cause death. Cause of death: cardiac arrhythmia from MDPV intoxication. bkt001
Wright et al. (2013) reported two fatalities with blood concentrations of 39 and 130 ng/mL. Recreationally encountered blood concentrations range from 24–241 ng/mL.supported
Two MDPV deaths; blood concentrations 39 and 130 ng/mL... Recreational blood range: 24-241 ng/mL 1556-4029.12260
Wright et al. (2013) reported two fatalities with blood concentrations of 39 and 130 ng/mL. Recreationally encountered blood concentrations range from 24–241 ng/mL.supported
Two MDPV deaths; blood concentrations 39 and 130 ng/mL... Recreational blood range: 24-241 ng/mL 1556-4029.12260
Desharnais et al. (2017) documented a fatal idiosyncratic reaction at only 6 ng/mL blood MDPV — far below the recreational range — via excited delirium progressing to cardiac arrest.supported
Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic). Excited delirium syndrome. s12024-017-9894-1
Rat studies showed no overt acute toxicity at subcutaneous doses up to 4 mg/kgsupported
4 mg/kg: stereotypy and disrupted PPI. Moderate hyperthermia exacerbated in group-housed animals. fpsyt.2018.00144
The cardiotoxic EC₅₀ was 228 μM, approximately 90-fold higher than the neurobehavioral EC₅₀ of 2.51 μM — indicating that cardiotoxicity requires substantially higher concentrations than behavioral effects in this modelsupported
MDPV causes concentration-dependent bradycardia and AV conduction block (EC50=228μM cardiotoxic); locomotor EC50=2.51μM. Cardiotoxic thresholds nearly 100x higher than neurobehavioral effects. ijms27010059
Claim in safety — inconclusiveinconclusiveworking →
Acute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.supported
hallucinations/delusions (26.7%) s13181-012-0243-1
Acute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.supported
delusions/hallucinations 40% pmid:21597456
Acute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.supported
Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis j.amjmed.2012.02.019
Unusual perceptual disturbances — gustatory and olfactory hallucinations have been documented in at least one intravenous case.supported
gustatory and olfactory hallucinations pmid:24356039
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Chronic psychiatric effects — repeated MDPV use is associated with acute psychosis, hypomania, paranoid ideation, and persistent delusions.supported
Chronic cathinone use induces acute psychosis, hypomania, paranoid ideation, delusions similar to ATS effects. fpsyt.2017.00156
Suicidal ideation and self-mutilation — documented in clinical presentations.supported
suicidal ideation, self-mutilation, violent behavior j.amjmed.2012.02.019
Claim in safety — inconclusiveinconclusiveworking →
Acute tolerance develops rapidly through DAT downregulation and membrane internalization in striatal tissuesupported
MDPV downregulated DAT in striatum and produced shift in subcellular distribution 24h post-dose j.neuropharm.2018.04.031
Prolonged brain network reorganization — increased clustering and altered functional connectivity patterns persisting 24 hours post-exposure — suggests that neuroadaptive changes extend well beyond the acute pharmacokinetic window.supported
prolonged brain functional network reorganization. Increased clustering coefficient, rich club index. j.neuropharm.2018.04.031
MDPV maintains intravenous self-administration at all doses tested (0.05–0.2 mg/kg/infusion) in rats.supported
MDPV maintained IVSA across all doses (0.05, 0.1, 0.2 mg/kg/infusion). j.1369-1600.2012.00474.x
Under long-access conditions (6 hr/day), rats escalate MDPV intake at rates comparable to methamphetamine.supported
Long-access conditions led to escalation of intake similar to methamphetamine. j.1369-1600.2012.00474.x
Claim in safety — inconclusiveinconclusiveworking →
MDPV lowers ICSS reward thresholds at all tested doses (0.1–2.0 mg/kg IP).supported
MDPV lowered ICSS thresholds at all doses (0.1-2 mg/kg IP). j.1369-1600.2012.00474.x
Inhaled MDPV (via e-cigarette model) produces locomotor stimulation and ICSS threshold reduction comparable to intraperitoneal injection.supported
inhaled MDPV (25-100 mg/mL) increased locomotor activity... MDPV vapor reduced ICSS reward threshold comparable to IP injection of 0.5-1.0 mg/kg. npp.2016.88
Clinical evidence confirms MDPV addiction as a real-world phenomenon: Casati et al. (2025) documented a 58-year-old with established MDPV addiction in a polydrug fatality casesupported
Fatal case: 58-year-old with history of MDPV addiction found dead... Confirms MDPV addiction history bkaf048
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The tramadol interaction carries the additional risk of seizure threshold lowering (tramadol's known epileptogenic potential) compounded by MDPV's documented seizure risk.supported
rhabdomyolysis, seizures, stroke, cerebral edema, MI, death j.amjmed.2012.02.019
MDPV's metabolism via CYP2C19, CYP2D6, and CYP1A2 creates theoretical risk of elevated MDPV exposure when coadministered with inhibitors of these enzymessupported
CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step. jms.1859
Management is supportive and extrapolated from cocaine/amphetamine toxidrome protocols: * IV benzodiazepines for agitation and seizure control (first-line) * Aggressive external cooling for hyperthermia * IV fluid resuscitation for rhabdomyolysis and renal protection * Small-dose haloperidol for choreoathetoid movements not controlled by benzodiazepines * ICU monitoring for cardiac, renal, and hepatic function * Physical restraints for imminent self-harm or violencesupported
adverse effects: tachycardia, hypertension, agitation, seizures, paranoia, hallucinations, hyperthermia, metabolic acidosis, rhabdomyolysis; no specific antidote. sar.s37257
Management is supportive and extrapolated from cocaine/amphetamine toxidrome protocols: * IV benzodiazepines for agitation and seizure control (first-line) * Aggressive external cooling for hyperthermia * IV fluid resuscitation for rhabdomyolysis and renal protection * Small-dose haloperidol for choreoathetoid movements not controlled by benzodiazepines * ICU monitoring for cardiac, renal, and hepatic function * Physical restraints for imminent self-harm or violencesupported
Treatment: benzodiazepines (46%), haloperidol for agitation. s13181-012-0243-1
Absolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.supported
Physical: tachycardia, hypertension, arrhythmias, hyperthermia... Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis j.amjmed.2012.02.019
Absolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.supported
tachycardia (53.3%), agitation (50.4%), hallucinations/delusions (26.7%), hypertension (25.2%) s13181-012-0243-1
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Relative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal riskssupported
Chronic cathinone use induces acute psychosis, hypomania, paranoid ideation, delusions similar to ATS effects. fpsyt.2017.00156
Relative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal riskssupported
rhabdomyolysis, cardiac injury, hepatic injury, renal failure j.annemergmed.2012.01.005
Relative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal riskssupported
acute kidney injury (creatinine 15.2 mg/dL) pmid:24356039
Relative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal riskssupported
hepatic injury, renal failure j.annemergmed.2012.01.005
Relative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal riskssupported
rhabdomyolysis, seizures, stroke, cerebral edema, MI, death j.amjmed.2012.02.019
pharmacology23 · 20 ok
Ten Phase I metabolites have been identified in human liver microsomes:supported
MDPV: 10 Phase I metabolites (reduction, hydroxylation, pyrrolidine ring loss). s00216-015-8763-6
In rat synaptosomal preparations, racemic MDPV inhibits dopamine uptake with IC₅₀ = 4.1 nM and norepinephrine uptake with IC₅₀ = 26 nM, compared to IC₅₀ = 3,349 nM at SERT — a DAT/SERT selectivity ratio exceeding 800-fold.supported
MDPV blocks uptake of [3H]dopamine (IC50=4.1 nM) and [3H]norepinephrine (IC50=26 nM) with high potency but has weak effects on [3H]serotonin (IC50=3349 nM). npp.2012.204
This distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releaserssupported
Not a transporter substrate. npp.2012.204
This distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releaserssupported
unlike amphetamines did not evoke release of monoamines. j.1476-5381.2012.02145.x
This distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releaserssupported
like cocaine, did not induce transporter-mediated release. j.bcp.2013.04.004
MDPV also exhibits high-nanomolar to low-micromolar affinity at sigma-1 (σ₁) receptors, though this binding is unlikely to account for its primary psychoactive effects at recreational dosessupported
high-nanomolar to micromolar affinity for hSigma1. j.bcp.2013.04.004
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
At subcutaneous doses of 0.1–3.0 mg/kg, MDPV is at least 10-fold more potent than cocaine at producing locomotor activation, tachycardia, and hypertensionsupported
MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. npp.2012.204
Claim in pharmacology — inconclusiveinconclusiveworking →
In rats receiving subcutaneous MDPV (0.5–2.0 mg/kg), pharmacokinetics are linear (dose-proportional) across the tested rangesupported
Linear PK: Cmax 74.2-271.3 μg/L at 0.5-2 mg/kg sc. adb.12201
Peak plasma concentrations (Tmax) occur at 12.9–18.6 minutes, with peak brain concentrations reached within 30 minutessupported
Tmax 12.9-18.6 min. adb.12201
Peak plasma concentrations (Tmax) occur at 12.9–18.6 minutes, with peak brain concentrations reached within 30 minutessupported
Peak concentrations in serum, brain, lung < 30 min. fpsyt.2018.00144
The brain-to-serum concentration ratio reaches approximately 2:1 and is sustained for approximately 120 minutes, indicating substantial CNS accumulationsupported
Brain/serum ratio ~2 lasting ~120 min. fpsyt.2018.00144
Plasma half-life is approximately 80 minutes in rats.supported
Elimination half-life ~80 min. fpsyt.2018.00144
Pharmacodynamic effects — locomotor activity and stereotypy — correlate with parent compound plasma concentrations, not with metabolite levels, confirming that MDPV itself is the active species.supported
Motor stimulation positively correlated with plasma MDPV, negatively with metabolites. adb.12201
Pharmacodynamic effects — locomotor activity and stereotypy — correlate with parent compound plasma concentrations, not with metabolite levels, confirming that MDPV itself is the active species.supported
Motor activation correlates with parent drug plasma levels, not metabolites. 7854_2016_53
The initial and rate-limiting step is demethylenation of the 3,4-methylenedioxy group, catalyzed by CYP2C19, CYP2D6, and CYP1A2.supported
CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step. jms.1859
3,4-Dihydroxypyrovalerone (3,4-catechol-PV) — the major Phase I metabolite. Retains potent DAT inhibition in vitro (IC₅₀ = 11 nM) but has poor CNS penetration, limiting its behavioral contribution.supported
3,4-catechol-PV (DAT IC50=11 nM, poor BBB penetration) 7854_2016_53
4-Hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) — the major circulating metabolite by AUC. Much weaker at DAT and NET; does not account for motor-stimulant effects.supported
4-OH-3-MeO-PV is predominant metabolite (highest AUC). Motor stimulation positively correlated with plasma MDPV, negatively with metabolites. adb.12201
Additional pathways include aromatic and side-chain hydroxylation, pyrrolidine ring oxidation to the lactam, and ring opening to the corresponding carboxylic acid.supported
aromatic and side chain hydroxylation, pyrrolidine ring oxidation to lactam, ring opening to carboxylic acid. jms.1859
Phase II metabolism produces 6 glucuronide and 2 sulfate conjugatessupported
6 glucuronidated and 2 sulphated Phase II metabolites identified. s00216-015-8763-6
In rat urine, the major excreted species are demethylenyl-MDPV and demethylenyl-methyl-MDPV, present at 3–4× higher concentrations than the parent drug.supported
Major urinary metabolites: demethylenyl-MDPV and demethylenyl-methyl-MDPV at 3-4x parent drug levels. fpsyt.2018.00144
summary12 · 10 ok
Active at oral doses as low as 2 mg — approximately 10-fold more potent than cocaine in animal models — MDPV produces intense stimulation lasting 2–8 hours depending on dose and route of administration.partially supported
MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. npp.2012.204
Active at oral doses as low as 2 mg — approximately 10-fold more potent than cocaine in animal models — MDPV produces intense stimulation lasting 2–8 hours depending on dose and route of administration.partially supported
Intoxication lasts 6-8 hours. j.amjmed.2012.02.019
First synthesized at Boehringer Ingelheim in 1969 and patented as a CNS stimulant (US Patent 3478050), MDPV was never clinically developedsupported
First synthesized by Boehringer Ingelheim in 1969; introduced on black market 2006. s12024-017-9894-1
MDPV blocks the dopamine transporter (DAT IC₅₀ = 4.1 nM) and norepinephrine transporter (NET IC₅₀ = 26 nM) with negligible serotonin transporter activity (SERT IC₅₀ = 3,349 nM)supported
MDPV blocks uptake of [3H]dopamine (IC50=4.1 nM) and [3H]norepinephrine (IC50=26 nM) with high potency but has weak effects on [3H]serotonin (IC50=3349 nM). npp.2012.204
Unlike mephedrone and methylone, MDPV functions exclusively as a reuptake inhibitor — it does not act as a transporter substrate and does not induce monoamine releasesupported
MDPV and pyrovalerone: highly potent and selective DA and NA transporter inhibitors; unlike amphetamines did not evoke release of monoamines. j.1476-5381.2012.02145.x
Four non-conserved residues in human DAT (A117, F318, P323, D121) account for this exceptional DAT selectivity.supported
Four non-conserved residues (A117, F318, P323, D121) control MDPV selectivity for hDAT. j.neuropharm.2021.108820
Compulsive redosing is a defining feature of the MDPV experience, observed across species and consistent with its potent activation of mesolimbic reward circuitrysupported
Long-access conditions led to escalation of intake similar to methamphetamine. MDPV lowered ICSS thresholds at all doses. High reinforcing properties and activation of brain reward circuitry. j.1369-1600.2012.00474.x
Acute toxicity is high: multiple fatalities are documented, including one idiosyncratic death at a blood concentration of only 6 ng/mLsupported
Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic). s12024-017-9894-1
Cardiovascular toxicity (tachycardia, hypertension, myocardial infarction), hyperthermia, rhabdomyolysis, acute kidney injury, and multiorgan failure appear in the clinical case literaturesupported
25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure. j.annemergmed.2012.01.005
Acute psychosis — paranoid delusions, hallucinations — occurs in 26–40% of emergency presentations and can persist after cessation, requiring electroconvulsive therapy in treatment-resistant casessupported
hallucinations/delusions (26.7%) s13181-012-0243-1
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
clinical-evidence10 · 8 ok
Multiorgan failure (IV route): Borek (2012) described hyperthermia and multiorgan failure following intravenous MDPV injection, highlighting the severe toxicity potential of parenteral administration.supported
25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure. j.annemergmed.2012.01.005
Idiosyncratic fatality: Desharnais et al. (2017) reported death via excited delirium and cardiac arrest at a blood MDPV concentration of only 6 ng/mL — far below recreationally encountered levels (24–241 ng/mL).supported
Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic). Excited delirium syndrome. s12024-017-9894-1
Idiosyncratic fatality: Desharnais et al. (2017) reported death via excited delirium and cardiac arrest at a blood MDPV concentration of only 6 ng/mL — far below recreationally encountered levels (24–241 ng/mL).supported
Recreational blood range: 24-241 ng/mL 1556-4029.12260
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The Michigan Department of Community Health documented a concentrated cluster of emergency department visits between November 2010 and March 2011, with tachycardia present in 63% of cases and agitation as the predominant presenting complaintsupported
35 Michigan ED bath salts cases (MDPV/mephedrone). Agitation 66%, tachycardia 63% pmid:21597456
Murphy et al. (2013) reported a regional poison center series in which hypertension was documented in 25% of cases and paranoia was a frequent psychiatric feature.supported
hypertension (25.2%)... hallucinations/delusions (26.7%) s13181-012-0243-1
Treatment is supportive: intravenous benzodiazepines for agitation and seizures, aggressive cooling for hyperthermia, IV fluid resuscitation for rhabdomyolysis, and ICU monitoring for cardiac and renal function.supported
Treatment: IV benzodiazepines, supportive care. j.amjmed.2012.02.019
Acute kidney injury with unusual sensory phenomena: Sutamtewagul et al. (2014) reported an IV MDPV case presenting with sympathomimetic syndrome, choreoathetoid movements, gustatory and olfactory hallucinations, and acute kidney injury.supported
IV MDPV bath salts: sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, acute kidney injury (creatinine 15.2 mg/dL). pmid:24356039
Claim in clinical-evidence — inconclusiveinconclusiveworking →
MDPV is not detected by routine immunoassay urine drug screenssupported
Not detected by routine drug screens. j.amjmed.2012.02.019
neuroscience6 · 2 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Intravenous MDPV (0.1–0.3 mg/kg) significantly elevates extracellular dopamine in the rat nucleus accumbens, and MDPV lowers intracranial self-stimulation (ICSS) reward thresholds at all doses tested (0.1–2.0 mg/kg IP), confirming robust activation of brain reward circuitrysupported
MDPV lowered ICSS thresholds at all doses (0.1-2 mg/kg IP). High reinforcing properties and activation of brain reward circuitry. j.1369-1600.2012.00474.x
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Colon-Perez et al. (2018) demonstrated that a single acute MDPV exposure produces prolonged reorganization of brain functional connectivity at 24 hours post-dose: increased network clustering, altered modularity, and shifted connectivity patterns that persist well beyond the pharmacokinetic elimination of the drugsupported
prolonged brain functional network reorganization. Increased clustering coefficient, rich club index. j.neuropharm.2018.04.031
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail6 · 6 ok
The linear PK profile across the 0.5–2.0 mg/kg subcutaneous dose range in rats suggests that saturation of metabolic or distributional processes does not occur at these dosessupported
Linear PK: Cmax 74.2-271.3 μg/L at 0.5-2 mg/kg sc. adb.12201
MDPV's dependence on CYP2C19, CYP2D6, and CYP1A2 for primary metabolism creates theoretical risk for pharmacokinetic interactionssupported
CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step. jms.1859
MDPV's brain-to-serum ratio of approximately 2:1, sustained for roughly 120 minutes post-dose, indicates preferential CNS accumulationsupported
Brain/serum ratio ~2 lasting ~120 min. fpsyt.2018.00144
This is consistent with MDPV's high lipophilicity and its ranking among the most BBB-permeable cathinones in in vitro modelssupported
MDPV exhibited particularly high blood-brain barrier permeability. j.1476-5381.2012.02145.x
The catechol metabolite (3,4-dihydroxypyrovalerone) retains potent DAT inhibition in vitro (IC₅₀ = 11 nM) but demonstrates poor CNS penetration, limiting its contribution to behavioral effectssupported
3,4-catechol-PV (DAT IC50=11 nM, poor BBB penetration) 7854_2016_53
Pharmacodynamic effects correlate with parent MDPV plasma concentrations, not metabolite levels, across all measured behavioral endpoints.supported
Motor stimulation positively correlated with plasma MDPV, negatively with metabolites. adb.12201
history5 · 2 ok
Boehringer Sohn AG and Boehringer Ingelheim GmbH)supported
First synthesized by Boehringer Ingelheim in 1969 s12024-017-9894-1
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Emergency department presentations surged: the Michigan Department of Community Health documented a rapid cluster of cases between November 2010 and March 2011, and regional poison centers across the US reported exponential growth in synthetic cathinone exposuressupported
35 Michigan ED bath salts cases (MDPV/mephedrone)... Emergency public health order issued. pmid:21597456
Claim in history — not_supportednot supportedworking →
chemistry4 · 2 ok
Claim in chemistry — inconclusiveinconclusiveworking →
The pyrrolidine ring confers high lipophilicity and steric bulk at the amine, which is critical for MDPV's function as a reuptake inhibitor rather than a transporter substrate — pyrrolidine-containing cathinones consistently fail to induce monoamine release.supported
Not a transporter substrate. npp.2012.204
Enantioselective pharmacology reveals a striking potency differential: the S-enantiomer is approximately 100-fold more potent than the R-enantiomer at the dopamine transporter (S-MDPV DAT IC₅₀ = 2.1 nM; R-MDPV DAT IC₅₀ = 382 nM)supported
S-isomer DAT IC50=2.1 nM vs R-isomer 382 nM (~100x selectivity). 7854_2016_53
Claim in chemistry — inconclusiveinconclusiveworking →
comparative-pharmacology4 · 4 ok
MDPV and cocaine share a common mechanism as DAT/NET reuptake inhibitors, but MDPV is approximately 50-fold more potent at human DAT and at least 10-fold more potent than cocaine in producing locomotor activation, tachycardia, and hypertension in ratssupported
MDPV ~50-fold more potent than cocaine at hDAT j.neuropharm.2021.108820
MDPV and cocaine share a common mechanism as DAT/NET reuptake inhibitors, but MDPV is approximately 50-fold more potent at human DAT and at least 10-fold more potent than cocaine in producing locomotor activation, tachycardia, and hypertension in ratssupported
MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. npp.2012.204
The mechanistic divide between MDPV (pure inhibitor) and mephedrone/methylone (substrate-type releasers) produces qualitatively different pharmacological and subjective profilessupported
highly potent and selective DA and NA transporter inhibitors; unlike amphetamines did not evoke release of monoamines. j.1476-5381.2012.02145.x
In long-access self-administration paradigms (6 hours/day), rats escalate MDPV intake at rates comparable to methamphetaminesupported
Long-access conditions led to escalation of intake similar to methamphetamine. j.1369-1600.2012.00474.x
receptor-pharmacology3 · 2 ok
Steele et al. (2021) identified four non-conserved residues in the human DAT — A117, F318, P323, and D121 — that dictate MDPV's exceptional selectivity for hDAT over both dDAT (Drosophila DAT, used as a structural proxy) and hSERTsupported
Four non-conserved residues (A117, F318, P323, D121) control MDPV selectivity for hDAT. j.neuropharm.2021.108820
MDPV exhibits binding at sigma-1 (σ₁) receptors in the high-nanomolar to low-micromolar rangesupported
high-nanomolar to micromolar affinity for hSigma1. j.bcp.2013.04.004
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →