Claim in safety — not_supportednot supportedworking →
Claim in safety — not_supportednot supportedworking →
Both documented clinical cases involved polysubstance use — a 34-year-old male with confusion, agitation, and inability to follow commands (concurrent amitriptyline, nortriptyline, nicotine) and a 26-year-old female with intrauterine fetal death (concurrent cannabinoids, cocaine, nicotine, hydrocodone) — preventing isolation of prolintane's individual toxicological contribution.supported
Case 1: 34yo male, confused and agitated, GC-MS positive for prolintane, amitriptyline, nortriptyline, nicotine. Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone. pmid:17725890
Jeong et al. (2023) evaluated prolintane's cardiac safety in mice and rats and documented hERG potassium channel inhibition — the canonical biomarker for drug-induced QT interval prolongation and ventricular arrhythmia risksupported
QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk. 01480545.2022.2049289
The authors concluded that prolintane "cannot be excluded" from causing ventricular arrhythmia risk.supported
QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk. Not directly myocardiotoxic. 01480545.2022.2049289
At therapeutic oral doses (10–20 mg), prolintane produced minimal cardiovascular changes in a controlled human comparison study, in contrast to ephedrinesupported
Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR). Doses in 10-20mg range commonly used medically. pmid:6471970
Jeong et al. (2023) documented shortened IBA-1 immunoreactive process length in rodent brain following prolintane administration — a marker of microglial activation and neuroinflammation that may disrupt synaptic contactssupported
IHC showed shortened IBA-1 (microglial marker) length suggesting neuroinflammation. 01480545.2022.2049289
Reduced motor coordination was observed in both mice and ratssupported
Prolintane reduced motor coordination in rodents. 01480545.2022.2049289
Prolintane was detected in a case involving intrauterine fetal death, though polysubstance use (cannabinoids, cocaine, nicotine, hydrocodone) prevents causal attributionsupported
Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone. pmid:17725890
Claim in safety — not_supportednot supportedworking →
Visual hallucinations have been documented with prolintane use in two contexts: overdose settings and chronic therapeutic-dose combination with diphenhydraminesupported
Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses. pmid:11819155
Claim in safety — not_supportednot supportedworking →
The hallucinations observed with prolintane-diphenhydramine combination at therapeutic doses developed over a 2-month period and were attributed to pharmacological kindling — progressive sensitization of dopaminergic pathways producing hallucinatory experiences at doses that were initially well-tolerated.supported
Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses... Pharmacological kindling proposed. pmid:11819155
Claim in safety — not_supportednot supportedworking →
Dose-dependent REM sleep suppression is confirmed in controlled studies, and extended wakefulness at higher doses (15–30 mg) may precipitate sleep-deprivation-related psychological disturbance.supported
Prolintane 15 and 30mg reduced REM sleep... Increased awakenings early in the night at higher doses. EEG-confirmed sleep disruption. pmid:7437258
Lee et al. (2022) conducted the first systematic evaluation of prolintane's abuse potential in rodents:supported
Prolintane increased locomotor activity, produced conditioned place preference, supported intravenous self-administration, and partially substituted for cocaine in drug discrimination. j.neuropharm.2021.108917
The authors concluded that prolintane possesses "a certain level of abuse potential" comparable to cocaine at a moderate level.supported
Results indicate moderate abuse potential similar to cocaine at moderate level. j.neuropharm.2021.108917
The historical discontinuation of prolintane from pharmaceutical markets was explicitly motivated by concerns about abuse liability.supported
its medical use was discontinued due to concerns about abuse liability. j.jbc.2025.110903
Prolintane also inhibits NET and, at human transporters, releases serotonin via SERT substrate activitysupported
Prolintane analogs display potent uptake inhibition at DAT and NET... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux. j.jbc.2025.110903
Deaths from tramadol combined with multiple serotonergic agents have been documented.supported
Case report of death of 36-year-old from seizure activity while taking tramadol combined with venlafaxine, trazodone, and quetiapine. pmid:11111800
Claim in safety — not_supportednot supportedworking →
mdma is a potent serotonin, dopamine, and norepinephrine releaser that can cause serotonin syndrome and hyperthermia at high dosessupported
MDMA is a potent releaser/reuptake inhibitor of serotonin, dopamine, and norepinephrine. Acute toxic effects include serotonin syndrome (muscle rigidity, hyperreflexia, hyperthermia). pmid:15228154
The combination of prolintane and diphenhydramine at therapeutic doses produced visual hallucinations in one documented case after 2 months of concurrent usesupported
Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses. pmid:11819155
Given prolintane's documented hERG channel inhibition in rodent models, combination with other QT-prolonging drugs (antiarrhythmics, certain antibiotics, antipsychotics, methadone) carries additive risk of ventricular arrhythmia.supported
QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk. 01480545.2022.2049289
Cardiac conduction disorders (absolute): Prolintane inhibits the hERG potassium channel and prolongs the QT interval in rodent modelssupported
QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk. 01480545.2022.2049289
Pregnancy (absolute): Prolintane was detected in a case of intrauterine fetal deathsupported
Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone. pmid:17725890
Hallucinations and psychosis are documented overdose outcomes, and hallucinations occurred at therapeutic doses in combination with diphenhydramine.partially supported
Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses. pmid:11819155
Concurrent serotonergic medication (relative to absolute, depending on agent): The SERT substrate activity at human transporters creates serotonin syndrome risk when combined with SSRIs, SNRIs, MAOIs, tramadol, or other serotonergic agents.supported
Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters. j.jbc.2025.110903
Cardiovascular disease (relative): While therapeutic doses (10–20 mg) produced minimal cardiovascular effects, the hERG inhibition data and dose-dependent risk profile warrant caution in individuals with pre-existing cardiovascular conditions.supported
Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR). Doses in 10-20mg range commonly used medically. pmid:6471970