generation run 2026-05-12
76 min completedmodel pipeline-v5plan not recordedrun/60a3de8c…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- safety_note
Reproduce
- inputs
- 45 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
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | methaqualone South Africa Mandrax abuse prevalence | 10 | 10 | Epidemiological data on methaqualone abuse in South Africa, which is the main remaining active market |
| 2 | PubMed | methaqualone pharmacokinetics metabolism half-life | 6 | 5 | Human pharmacokinetic and metabolism data |
| 3 | PubMed | methaqualone drug interactions alcohol CNS depressants combination | 6 | 4 | Drug interaction data between methaqualone and alcohol/other depressants |
| 4 | PubChem | methaqualone | 1 | 1 | Primary chemical identity verification |
| 5 | OpenAlex | methaqualone Quaalude abuse recreational drug 1970s history | 4 | 1 | SL-164 analog case report relevant for new designer drug context |
| 6 | OpenAlex | methaqualone quinazolinone sedative hypnotic | 10 | 3 | Selected papers directly relevant to methaqualone pharmacology |
| 7 | PubMed | methaqualone metabolism cytochrome P450 CYP liver | 1 | 1 | Key CYP enzyme data for methaqualone metabolism |
| 8 | ClinicalTrials.gov · absence | methaqualone | 0 | 0 | No relevant trials - methaqualone is Schedule I in US, no current clinical development |
| 9 | PubMed | methaqualone pharmacology GABA receptor mechanism | 6 | 6 | All directly relevant to methaqualone pharmacology |
| 10 | PubMed | PMID 10165 | 1 | 1 | Human pharmacokinetic parameters |
| 11 | WebSearch | methaqualone half-life plasma protein binding volume distribution pharmacokinetics | 10 | 2 | PK parameters synthesis |
| 12 | PubMed | methaqualone urinary metabolites 4-hydroxymethaqualone | 3 | 2 | Metabolite characterization |
| 13 | PubMed | methaqualone plasma levels oral absorption Morris 1972 | 1 | 1 | Original PK absorption paper |
| 14 | PubChem REST API | CID 6292 properties | 1 | 3 | Chemical identity verification |
| 15 | WebSearch | methaqualone Quaalude brand names Lemmon Company commercial history | 10 | 2 | Commercial/brand history |
| 16 | WebSearch | methaqualone Kacker Zaheer 1951 synthesis discovery India | 10 | 2 | Discovery history |
| 17 | Erowid Timeline | — | 1 | 1 | Historical chronology |
| 18 | WebSearch | methaqualone Schedule I DEA scheduling history 1973 | 10 | 2 | Legal scheduling history |
| 19 | WebSearch | methaqualone legal status UK Canada Australia EU scheduling | 10 | 2 | International legal status |
| 20 | PubMed | PMID 6130076 | 1 | 1 | Human abuse liability data |
| 21 | WebSearch | methaqualone physical properties melting point solubility | 10 | 1 | Physical property verification |
| 22 | WebSearch | methaqualone smoked white pipe South Africa pharmacokinetics | 10 | 2 | Smoked ROA characterization |
98 claims by section — every cited sentence, checked against its source
safety32 · 23 ok
The only published LD50 for methaqualone is 240 mg/kg (intraperitoneal, mouse)supported
Mouse LD50 for methaqualone 240 mg/kg. pmid:493294
Doses exceeding 300 mg oral may produce dangerous effects in individuals without tolerance, though this threshold lacks formal determination in dose-escalation studiessupported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. pmid:6130076
Claim in safety — inconclusiveinconclusiveworking →
All GABAA-active agents — benzodiazepines, barbiturates, GHB, neurosteroids, anesthetic agents — carry additive or synergistic risk of respiratory depression in combination with methaqualonesupported
Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes. jcph.1922
In a series of 349 acute poisoning cases involving non-barbiturate hypnotics, Ruedy (1973) found unconsciousness and respiratory depression as the most common features, with 6 deaths and 5 surviving patients remaining unconscious for more than 24 hours.partially supported
Prospective study of 349 poisoning patients; non-barbiturate hypnotics most frequent; unconsciousness, respiratory depression, metabolic acidosis most common findings. 6 deaths. pmid:4742490
Claim in safety — inconclusiveinconclusiveworking →
Dose-dependent respiratory depression is the primary life-threatening effect, shared with all GABAA positive allosteric modulatorssupported
Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes. jcph.1922
No antidote is established for clinical use; naloxone (10 mg/kg in mice) partially antagonized methaqualone lethality, but the mechanism remains unclear and naloxone is not a standard treatment for methaqualone overdose in humans.supported
Mouse LD50 for methaqualone 240 mg/kg; naloxone increased LD50 to 416 mg/kg. pmid:493294
Haider and Oswald (1970) described a late withdrawal syndrome occurring 1–3 weeks after methaqualone overdose: insomnia, restlessness, elevated REM sleep, epileptic phenomena, and deliriumsupported
Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium. pmid:4317051
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In the South African context, methaqualone (Mandrax) use is epidemiologically associated with sexual risk-taking, reduced ability to negotiate safer sex, increased HIV transmission risk, and drug-facilitated sexual assault.partially supported
Methaqualone identified as substance used in drug-facilitated sexual assault. Toxicological screening not routinely available in clinical forensic practice in Western Cape. j.forsciint.2018.04.028
The compound's documented high abuse liability and compulsive redosing urge contribute to a pattern of escalating use. Euphoria reinforces repeated administration, while amnesia may mask the extent of impairment from the user's perspective.partially supported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. pmid:6130076
Pharmacodynamic tolerance: GABAA receptor adaptation at the cellular level. In mice, continuous methaqualone exposure produces measurable tolerance (significantly reduced sleep-times) within 36 days.supported
Tolerance and physical dependence produced in mice after 36 days exposure via food pellets. Tolerance shown by reduced sleep-times. pmid:1239784
Pharmacokinetic tolerance: CYP3A4 enzyme induction increases the rate of methaqualone metabolism. In clinically dependent Mandrax patients, hepatic drug-metabolizing capacity was the highest measured for any drug-exposed group — manifested as the shortest antipyrine half-life reported in the literature for drug-exposed individuals.partially supported
3 Mandrax-dependent patients studied; very high drug-metabolizing capacity on admission; marked drug tolerance. Induction of drug-metabolizing capacity contributed to tolerance. pmid:5085238
Physical dependence has been confirmed in mice, rats, and humanspartially supported
Tolerance and physical dependence produced in mice after 36 days exposure via food pellets. pmid:1239784
Claim in safety — inconclusiveinconclusiveworking →
Physical dependence has been confirmed in mice, rats, and humanssupported
3 Mandrax-dependent patients studied; very high drug-metabolizing capacity on admission; marked drug tolerance. pmid:5085238
Epileptic phenomena and delirium — documented 1–3 weeks post-exposuresupported
Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium. pmid:4317051
Cross-tolerance with barbiturates has been demonstrated: Mandrax-dependent animals show reduced sensitivity to pentobarbital-induced sleepsupported
Animals withdrawn from chronic Mandrax (methaqualone:diphenhydramine 10:1) showed significant cross-tolerance to intracerebroventricularly administered pentobarbital. pmid:4155651
Cole et al. (1982) demonstrated significantly elevated euphoria and abuse-liability scores compared to placebo in recreational sedative users, with a euphoriant profile exceeding that of diazepam at tested doses.supported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect. pmid:6130076
The interaction operates through pharmacodynamic sensitization: ethanol reduces the minimum effective dose of methaqualone at the target organ level, independent of any pharmacokinetic alteration of methaqualone distribution or eliminationsupported
Ethanol increases duration of methaqualone hypnosis via pharmacodynamic sensitization (reduced minimum effective dose) not altered PK. Methaqualone distribution and elimination unaffected by ethanol. pmid:644120
Claim in safety — inconclusiveinconclusiveworking →
{{Warning}}The alcohol-methaqualone interaction persists for at least 3 days after a single therapeutic dose of methaqualonesupported
Alcohol interaction with Mandrax apparent in Stroop test and visual analogue scale up to 3 days post-dose. pmid:892953
In mouse models, methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269%supported
Methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269%. pmid:493294
The in vitro mechanism involves synergistic inhibition of brain Na-K-ATPase, with greatest inhibition at low K+ and high Na+ ratios.supported
Combined methaqualone + ethanol inhibits brain Na-K-ATPase in mixed/non-competitive manner, with greatest effect at low K+/high Na+ ratios. pmid:6260047
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Concurrent use of other CNS depressants (alcohol, benzodiazepines, barbiturates, opioids, GHB, baclofen): Synergistic respiratory depression risk renders any combination potentially lethal.supported
Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes. jcph.1922
Claim in safety — inconclusiveinconclusiveworking →
Pregnancy: Methaqualone crosses the placental barrier; pharmacokinetics are altered during pregnancy and labour.partially supported
Methaqualone half-life prolonged during labour; diminished in pregnancy compared to non-pregnant controls. pmid:6933942
History of substance use disorders: High abuse liability and compulsive redosing potential make methaqualone contraindicated in individuals with vulnerability to substance dependence.supported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. pmid:6130076
pharmacology16 · 13 ok
Methaqualone acts as a positive allosteric modulator (PAM) of GABAA receptors — the principal inhibitory ligand-gated ion channels in the central nervous systemsupported
Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors. mol.115.099291
Unlike benzodiazepines, barbiturates, or neurosteroids, methaqualone binds at the transmembrane β(+)/α(−) subunit interface, the same site occupied by the general anesthetic etomidatesupported
Acts through transmembrane beta+/alpha- subunit interface overlapping with etomidate site. mol.115.099291
This binding site was definitively localized in 2024 through cryo-electron microscopy at atomic resolution, which demonstrated that methaqualone and its more potent derivative PPTQ insert more deeply into the intersubunit interface than either propofol or etomidate, widening the extracellular half of the ion-conducting pore and destabilizing the hydrophobic activation gate.supported
Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate. Binding results in widening of ion-conducting pore, destabilizing hydrophobic activation gate. s41467-024-49471-y
Methaqualone displays negligible activity at a broad panel of non-GABAA CNS targets, including other neurotransmitter receptors and transporterssupported
Negligible activity at other CNS targets. mol.115.099291
In vivo, the compound selectively antagonizes GABA-deficiency-induced convulsions (isoniazid model) in mice but does not block strychnine-induced convulsions (a glycine-receptor model), confirming GABAergic rather than glycinergic specificitysupported
Methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine. pmid:96460
The dose-response profile in mice is hierarchical: anticonvulsant activity appears at low, non-sedative doses, while muscle relaxation and sedation emerge at higher doses.supported
Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses. pmid:96460
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Peak serum concentrations of approximately 1.2 µg/mL occur 2–3 hours after a 250 mg oral dosesupported
After 250 mg oral dose, peak serum concentration 1.2 µg/mL at Tmax 3h. After 5th consecutive daily dose, peak 1.9 µg/mL at Tmax 2h. pmid:10165
Hepatic metabolism accounts for >95% of elimination, with less than 5% of the parent compound excreted unchanged in urinesupported
<1% excreted unchanged. pmid:21773
CYP3A4 is the primary metabolizing enzyme, producing the major metabolite 4ʹ-hydroxymethaqualone along with four additional monohydroxylated metabolites (2ʹ-OH, 3ʹ-OH, 2-OH, and 6-OH) and methaqualone-N1-oxidesupported
Five major monohydroxy metabolites; 4'-hydroxymethaqualone is major urinary metabolite. CYP3A4 is primary metabolic enzyme; CYP2D6 and CYP2C19 not significant contributors. pmid:12900872
CYP3A4 is the primary metabolizing enzyme, producing the major metabolite 4ʹ-hydroxymethaqualone along with four additional monohydroxylated metabolites (2ʹ-OH, 3ʹ-OH, 2-OH, and 6-OH) and methaqualone-N1-oxidepartially supported
Five monohydroxy metabolites identified. Main metabolite is conjugated 4'-hydroxymethaqualone. Methaqualone-N1-oxide confirmed as important metabolite. pmid:21773
CYP3A4 is the primary metabolizing enzyme, producing the major metabolite 4ʹ-hydroxymethaqualone along with four additional monohydroxylated metabolites (2ʹ-OH, 3ʹ-OH, 2-OH, and 6-OH) and methaqualone-N1-oxidepartially supported
Five monohydroxy metabolites: 4'-OH-MQ (major), 2'-OH-MQ, 3'-OH-MQ, 2-OH-MQ, 6-OH-MQ. pmid:11589290
Metabolite excretion continues for at least 70 hours post-dose.supported
Metabolite excretion ongoing at 70h. pmid:21773
The elimination half-life is reported as approximately 10 hours by White et al. following repeated 250 mg oral dosing, though pharmacological reference sources cite values of 20–60 hourssupported
Half-life ~10h. No significant accumulation over 5 days. pmid:10165
Claim in pharmacology — inconclusiveinconclusiveworking →
summary13 · 11 ok
Claim in summary — inconclusiveinconclusiveworking →
Moderate lipophilicity (XLogP 2.5) facilitates efficient blood-brain barrier penetration.partially supported
Review of quinazolinone pharmacology and structure-activity relationships. Covers CNS activity related to BBB penetration due to lipophilicity. molecules28030978
Controlled human studies confirmed high abuse liability relative to other sedatives, leading to progressive scheduling: Schedule II in the US (1973), then Schedule I (1984), with legal manufacture ceasing worldwidepartially supported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. pmid:6130076
The compound retains research significance through 2024 cryo-EM structural studies resolving its unique GABAA binding site, and it persists as a major illicit drug in South Africa.partially supported
Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate. s41467-024-49471-y
The compound retains research significance through 2024 cryo-EM structural studies resolving its unique GABAA binding site, and it persists as a major illicit drug in South Africa.supported
SACENDU surveillance network; methaqualone (Mandrax) one of the two most prevalent illicit drugs in South Africa 1997-1999. pmid:12144599
Methaqualone potentiates GABAA receptors through the transmembrane β(+)/α(−) subunit interface — the etomidate site — rather than through benzodiazepine, barbiturate, or neurosteroid binding sitessupported
Acts through transmembrane beta+/alpha- subunit interface overlapping with etomidate site. mol.115.099291
It displays positive allosteric modulation at α1,2,3,5β2,3γ2S subtypes and a complex, multifaceted profile at δ-containing extrasynaptic receptors ranging from negative modulation to superagonism — a selectivity pattern without parallel among clinically used GABAergics.supported
Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes. mol.115.099291
The subjective experience centers on sedation, muscle-relaxation, and a distinctive euphoria with prominent tactile components — peripheral paresthesia in lips and fingertips, grounded in GABA-mediated modulation of somatosensory cortex receptive fields. disinhibition and anxiety-suppression complete the core profilesupported
Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes. Users report peripheral paresthesia and transient numbness in lips and fingertips. pmid:2311013
Mouse LD50 is 240 mg/kg intraperitoneally; overdose presents with respiratory depression, unconsciousness, and paradoxical convulsionspartially supported
Mouse LD50 for methaqualone 240 mg/kg; naloxone increased LD50 to 416 mg/kg. pmid:493294
Claim in summary — inconclusiveinconclusiveworking →
Alcohol synergizes with methaqualone through pharmacodynamic sensitization persisting up to three days after a single dosepartially supported
Ethanol increases duration of methaqualone hypnosis via pharmacodynamic sensitization (reduced minimum effective dose) not altered PK. pmid:644120
Tolerance develops through dual mechanisms: GABAA receptor adaptation and CYP3A4 enzyme induction — the latter producing the shortest antipyrine half-life reported for any drug-exposed group in clinical studies of dependent patientspartially supported
Very high drug-metabolizing capacity on admission; marked drug tolerance. Induction of drug-metabolizing capacity contributed to tolerance. pmid:5085238
The elimination half-life remains disputed (10 hours vs 20–60 hours), likely reflecting two-compartment pharmacokinetics not fully resolved in published studies.supported
Half-life ~10h. No significant accumulation over 5 days. pmid:10165
clinical-evidence9 · 4 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The most informative controlled human study is the abuse-liability assessment by Cole et al. (1982), a blinded crossover design comparing methaqualone (300 mg oral) against diazepam, buspirone, and placebo in 24 recreational sedative userssupported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect. pmid:6130076
White et al. (1976): Measured serum methaqualone concentrations after repeated oral administration of the combination formulation (methaqualone + diphenhydramine) in human subjects. Established Tmax of 2–3 hours, peak concentration of ~1.2 µg/mL after 250 mg, and terminal half-life of ~10 hours with no evidence of accumulation on daily dosing.supported
After 250 mg oral dose, peak serum concentration 1.2 µg/mL at Tmax 3h. After 5th consecutive daily dose, peak 1.9 µg/mL at Tmax 2h. Half-life ~10h. No significant accumulation over 5 days. pmid:10165
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Naik et al. (1978) established methaqualone's anticonvulsant profile in mice: selective antagonism of isoniazid-induced (GABA-deficiency) convulsions but not strychnine-induced (glycinergic) convulsions, with a dose-dependent progression from anticonvulsant activity at non-sedative doses to muscle relaxation and sedation at higher doses.supported
Methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine. Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses. pmid:96460
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Sexual risk and HIV: Bonner et al. (2022) found methaqualone use reduced the ability of young women to negotiate safer sex, increasing HIV risk. Tiemensma and Davies (2018) identified methaqualone as a substance implicated in drug-facilitated sexual assault in Cape Town.partially supported
Methaqualone identified as substance used in drug-facilitated sexual assault. Toxicological screening not routinely available in clinical forensic practice in Western Cape. j.forsciint.2018.04.028
neuroscience7 · 5 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Haider and Oswald (1970) documented a delayed withdrawal syndrome 1–3 weeks after methaqualone overdose — insomnia, restlessness, elevated REM sleep, epileptic phenomena, and deliriumsupported
Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium. pmid:4317051
Claim in neuroscience — inconclusiveinconclusiveworking →
Hicks et al. (1990) showed that methaqualone alters receptive-field sizes of neurons in primary somatosensory cortex (S1), expanding or contracting the area of skin surface from which individual neurons respondsupported
Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes. pmid:2311013
The compound produces muscle relaxation at doses above the anticonvulsant threshold but below the sedative-hypnotic threshold, suggesting differential sensitivity of motor circuit GABAA receptors compared to cortical populations.supported
Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses. pmid:96460
Methaqualone's euphoriant and reinforcing properties, confirmed by controlled human data, implicate GABAergic modulation of mesolimbic reward circuitrysupported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. pmid:6130076
This phenomenon may involve selective depression of inhibitory interneurons at high concentrations (disinhibition of excitatory circuits) or engagement of the compound's negative modulatory activity at specific δ-containing receptor subtypes (e.g., α6β1δ).supported
Diverse functionalities at alpha4,6 subtypes. mol.115.099291
pharmacokinetic-detail5 · 5 ok
~10 hours: Measured by White et al. (1976) after repeated 250 mg oral dosing with no evidence of drug accumulationsupported
Half-life ~10h. No significant accumulation over 5 days. pmid:10165
CYP3A4 is the primary enzyme responsible, with no significant contribution from CYP2D6 or CYP2C19supported
CYP3A4 is primary metabolic enzyme; CYP2D6 and CYP2C19 not significant contributors. pmid:12900872
All five monohydroxylated metabolites display stereoselective formation, with enantiomeric excess detectable by chiral capillary electrophoresispartially supported
Major metabolite 4'OH-MQ excreted almost exclusively as single enantiomer. Stereoselective metabolism characterized. pmid:11589290
Metabolites are excreted primarily as glucuronide conjugates, with ongoing urinary excretion detectable at 70 hours post-dose.supported
Main metabolite is conjugated 4'-hydroxymethaqualone. Metabolite excretion ongoing at 70h. pmid:21773
Pregnancy alters methaqualone pharmacokinetics: half-life is prolonged during labour and shortened during active pregnancy compared to non-pregnant controls.supported
Methaqualone half-life prolonged during labour; diminished in pregnancy compared to non-pregnant controls. pmid:6933942
comparative-pharmacology4 · 4 ok
The controlled human comparison (Cole et al. 1982) found methaqualone (300 mg) produced greater euphoria and higher abuse-liability scores than diazepam at its tested dose, suggesting a qualitatively different reinforcement profile.supported
Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect. pmid:6130076
The critical structural distinction is that methaqualone and its quinazolinone analogs insert more deeply into the β(+)/α(−) intersubunit interface than either propofol or etomidate, as resolved by cryo-EMpartially supported
Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate. s41467-024-49471-y
Cross-tolerance between the two classes occurs through shared downstream GABAA-mediated neuroadaptation despite the different binding sites.supported
Animals withdrawn from chronic Mandrax showed significant cross-tolerance to intracerebroventricularly administered pentobarbital — confirms cross-tolerance between methaqualone and barbiturates. pmid:4155651
The quinazolinone scaffold has produced at least one documented research chemical analog: SL-164, identified in a 2024 case report of intoxication requiring LC-QTOF-MS for identification because standard immunoassay panels did not detect itsupported
Case report: 22-year-old with altered mental status after SL-164 (methaqualone analog) intoxication. Serum concentration 390 ng/mL. dta.3792
receptor-pharmacology4 · 3 ok
The hallmark of methaqualone's receptor pharmacology is a multifaceted profile across GABAA receptor subtypes — a selectivity pattern that defies simple classification as a universal GABAA potentiator.supported
Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes. mol.115.099291
At δ-subunit-containing extrasynaptic receptors — mediators of tonic inhibition — methaqualone displays a complex and subunit-dependent range of activities:supported
Diverse functionalities at alpha4,6 subtypes. mol.115.099291
Cryo-EM structural data (2024) resolved the methaqualone binding pose within the GABAA receptor at atomic resolutionsupported
Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces. s41467-024-49471-y
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
chemistry3 · 2 ok
Methaqualone belongs to the quinazolinone chemical class — nitrogen-containing heterocyclic compounds comprising a benzene ring fused to a pyrimidinone ringsupported
Review of quinazolinone pharmacology and structure-activity relationships. molecules28030978
Claim in chemistry — inconclusiveinconclusiveworking →
The primary urinary metabolite, 4ʹ-hydroxymethaqualone, is excreted almost exclusively as a single enantiomer, reflecting the stereoselective orientation of the parent compound within the CYP3A4 active sitepartially supported
Five major monohydroxy metabolites; 4'-hydroxymethaqualone is major urinary metabolite. CYP3A4 is primary metabolic enzyme. pmid:12900872
history3 · 0 ok
effects-overview1 · 1 ok
This tactile component has a confirmed neural substrate in somatosensory cortex GABA modulationsupported
Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes. Users report peripheral paresthesia and transient numbness in lips and fingertips. pmid:2311013
legal-status1 · 1 ok
Legal pharmaceutical manufacture ceased globally following US reclassification to Schedule I in 1984; all current methaqualone is clandestinely manufactured.partially supported
Comprehensive review of controlled substances; explicitly names methaqualone as a Schedule I drug alongside heroin and LSD. neurolint13040059