MB under dual selective MAOI matches MB-alone COX-amnestic rescue
STATUS_LABEL: NEGATIVE
polarity: negative swarm_id: N13 card_sha256: 47204514b13099a7b65965d54e57d2c8aef2682fc6e1d5d2cd7692fd82e39e3b risk_class: research-discussion note: PASS_NEGATIVE — shipped as discussion (not claim/hypothesis). Soft-complete dual selective MAOI∩MB∩COX-amnestic empty/non-match; matched H2H remains UNKNOWN.
Claim
On a pre-registered cytochrome-oxidase / COX-inhibitor amnestic retention assay where parent methylene blue restores memory, methylene blue under concurrent dual selective MAO-A inhibitor (clorgyline-class) + selective MAO-B inhibitor (selegiline/rasagiline-class) matches MB-alone rescue — retention Δ >70% of MB-alone (or inside a pre-registered MB-equivalence band).
Why it matters
Closes occupancy-subtraction escape left open by N12 (dual-alone failure): even if combo alone fails, concurrent dual MAOI could still subtract MB rescue; N13 tests MB-under-dual vs MB-alone on the same COX-amnestic assay. If MB rescue were MAO-driven, dual occupancy should subtract; preferential redox / COX-facing framing predicts MB+dual matches MB-alone. Distinct from N12 (dual-alone), N10/N11 (single arms never co-dosed MB under MAOI), N5 (MAO-A generic WM), N8 (Azure B), N9 (redox-dead) — none ran MB-under-dual selective MAOI on this assay. Soft-claims: discussion — soft-complete 0; H2H UNKNOWN; N5–N12 ≠ proof — N12 dual-alone ≠ MB-under-dual preservation.
Mechanism sketch
Redox-vs-MAO assumption-kill on the COX-amnestic / metabolic-memory class: parent MB restores retention after COX inhibition and is a preferential reversible MAO-A inhibitor; selective MAO-A and MAO-B tools exist (clorgyline-class; rasagiline/selegiline-class) but no published MB-under-dual COX-amnestic retention H2H vs MB-alone. Occupancy-subtraction escape: N12 dual-alone failure left open that concurrent dual MAOI could still subtract MB rescue; N13 closes that escape on the same assay with an MB-alone positive-control arm. Competing caveats: occupancy / PK interaction (underperformance of MB+dual vs MB-alone could be off-target rather than MAO occupancy — assay MAO-A/B occupancy without a dosing card); soft-complete empty ≠ demonstrated match; MAO IC50 ≠ brain rescue PD; N5–N12 ≠ proof.
Prior art
- PMID 12384216 / DOI 10.1016/s0304-3940(02)00827-3 — low-dose MB restores spatial memory retention impaired by a cytochrome oxidase inhibitor (Callaway / Gonzalez-Lima class) — no MB-under-dual selective MAOI arm.
- PMID 21087672 / DOI 10.1016/j.neuroimage.2010.11.023 / PMC3026638 — MB beneficial network effects in an amnestic model (metabolic/network framing) — no MB-under-dual selective MAOI arm.
- PMID 17721552 / DOI 10.1038/sj.bjp.0707430 / PMC2078225 — MB potent reversible preferential MAO-A inhibition (serotonin-toxicity prediction; Ramsay 2007) — enzyme / isoform prior, not MB-under-dual COX-amnestic H2H.
- PMID 26142126 / DOI 10.1016/j.neurobiolaging.2015.05.009 — rasagiline (selective MAO-B-i) improves cognitive deficits and related cascades in aged mice (Weinreb 2015) — MAO-B tool prior, not MB-under-dual COX-amnestic retention vs MB-alone.
Baseline claimed
On a COX-inhibitor amnestic model where parent MB restores retention, MB under concurrent dual selective MAO-A-i + MAO-B-i matches MB-alone rescue (MAO occupancy does not subtract), or N5–N12 already closed MAO ownership / occupancy-subtraction of metabolic-memory rescue.
Baseline measured
MB COX-amnestic / amnestic-network rescue LITERATURE (PMID 12384216; 21087672). MB preferential reversible MAO-A inhibition LITERATURE (PMID 17721552). Rasagiline selective MAO-B tool LITERATURE (PMID 26142126). MB under concurrent dual selective MAO-A-i + MAO-B-i vs MB-alone on the same COX-amnestic rescue / retention panel UNKNOWN (soft-complete MB∩dual selective MAOI∩COX-amnestic = 0; adjacent EuropePMC noise are non-matches). MB+dual matches MB-alone (retention Δ >70% of MB-alone / inside MB-equivalence band) PREDICTION. N5–N12 do not already prove this — N12 dual-alone left occupancy-subtraction OPEN; N10/N11 never co-dosed MB under MAOI; N5 generic WM; N8 Azure B; N9 redox-dead; soft-complete empty ≠ match.
Actionable limitations
- Do not treat N5–N12 as proving N13 — N12 dual-alone failure ≠ MB-under-dual preservation; N10/N11 single arms never co-dosed MB under MAOI; N5 was A-biased / generic WM; N8/N9 ran metabolite / redox-dead arms; soft-complete empty ≠ demonstrated MB-under-dual match on COX-amnestic.
- MAO IC50 ≠ brain rescue PD — Ramsay is preferential MAO-A enzyme inhibition; Weinreb 26142126 is aged-cognition / cascades; clorgyline 26825854 is monoamine/affective HD — none is MB + dual selective MAOI on COX-amnestic retention vs MB-alone.
- Occupancy-subtraction escape + occupancy matching — do not collapse N12 into MB-under-dual proof; underperformance of MB+dual vs MB-alone could be PK / off-target rather than MAO occupancy; assay MAO-A/B occupancy / monoamine readout without a dosing card; use the same COX-inhibitor amnestic class where parent MB restores, with MB-alone as positive control. No dosing.
Method
propose-assay
Prediction variables
| name | kind | assay | threshold |
|---|---|---|---|
| MB_COX_amnestic_spatial_retention_rescue | LITERATURE | Low-dose MB restores spatial memory retention after cytochrome oxidase inhibitor (Callaway 2002) | MB restores retention impaired by COX inhibition (PMID 12384216) — no MB-under-dual selective MAOI comparator |
| MB_amnestic_network_effects | LITERATURE | MB beneficial network effects in an amnestic model (Rojas / Gonzalez-Lima 2011) | metabolic/network framing of MB amnestic benefit (PMID 21087672) — no MB-under-dual selective MAOI arm |
| MB_preferential_MAO_A_inhibition | LITERATURE | MB potent reversible preferential MAO-A inhibition (Ramsay 2007) | enzyme / isoform prior — mild-MAOI frame predicts dual occupancy might subtract if MAO-driven; redox frame predicts match (PMID 17721552) — not COX-amnestic H2H; no KD invented |
| rasagiline_selective_MAO_B_tool_prior | LITERATURE | Rasagiline improves cognitive deficits and related cascades in aged mice (Weinreb 2015) | selective MAO-B tool prior (PMID 26142126) — not MB-under-dual COX-amnestic retention vs MB-alone |
| same_COX_amnestic_MB_under_dual_selective_MAOI_vs_MB_alone_panel | UNKNOWN | Same COX-inhibitor amnestic / retention panel — MB + concurrent dual selective MAO-A-i (clorgyline-class) + MAO-B-i (selegiline/rasagiline-class) vs MB-alone (± optional dual-alone arm from N12 / MAO occupancy readout) | dedicated MB-under-dual vs MB-alone COX-amnestic rescue panel not found (soft-complete 0; EuropePMC noise non-matches) — UNKNOWN |
| MB_under_dual_matches_MB_alone_on_COX_amnestic_rescue | PREDICTION | Pre-registered COX-inhibitor amnestic spatial or discrimination retention; MB + clorgyline-class + selegiline/rasagiline-class vs MB-alone under exposure-aware conditions | MB+dual retention Δ >70% of MB-alone (or inside pre-registered MB-equivalence band); α/N pre-specified — do not invent observed Δ or dosing |
| competing_dual_occupancy_or_PK_subtracts_MB_rescue | PREDICTION | Same design; falsifier path if MB+dual underperforms MB-alone once MAO-A/B occupancy / brain exposure is matched | occupancy-matched subtraction / PK-matched underperformance allowed as pre-registered competing outcomes — does not invent those results |
Ablate
- remove same COX-amnestic / retention contrast of MB under concurrent dual selective MAO-A-i + MAO-B-i vs MB-alone: Without the behavioral H2H on the Gonzalez-Lima class assay with an MB-alone arm, MB rescue LITERATURE and dual-alone / single-isoform tool LITERATURE cannot show MB-under-dual matches MB-alone rescue.
- remove concurrent dual selective MAO-A + MAO-B identity (clorgyline-class + selegiline/rasagiline-class) co-dosed with parent MB under preferential-MAO-A / redox framing: Without a verified MB-under-dual selective MAOI co-panel, match/fail is just “another monoaminergic stack,” not an assumption-kill of MAO-occupancy necessity for MB COX-amnestic rescue or of occupancy-subtraction escape after N12.
- remove N5–N12≠proof + soft-complete-empty≠match + MAO-IC50≠brain-PD + occupancy-matching + N12-dual-alone≠MB-under-dual-proof discipline: Treating N5–N12 dual-alone / single-arm / metabolite / redox-dead cards or empty/adjacent PubMed or Ramsay/Weinreb enzyme-disease priors as already deciding MB-under-dual match would invent a positive result left UNKNOWN.
Refute if
On the pre-registered COX-inhibitor amnestic retention assay, MB under concurrent dual selective MAO-A-i + MAO-B-i fails to match MB-alone (retention Δ ≤70% of MB-alone or outside the MB-equivalence band) — especially under exposure/MAO-A/B-occupancy-matched conditions — so MAO-occupancy necessity for MB metabolic-memory rescue survives and redox-only framing fails.
Ask a human
Lock COX-inhibitor amnestic assay identity (spatial vs discrimination retention class where parent MB restores), MB-alone positive-control arm, clorgyline-class + selegiline/rasagiline-class dual selective MAOI tools concurrent with MB, exposure/MAO-A/B-occupancy readout, and optional N12 dual-alone arm before treating any MB metabolic-memory rescue as redox-owned vs MAO-occupancy-owned; do not treat N5–N12 as already proving MB-under-dual match; no dosing.
Cheap IP
kill_cost_tier=1 · time_to_refute=4w · ip_class=redox-vs-MAO · vault_hold=no
Execution
execution_status=NOT_RUN · fto_status=UNKNOWN · related_prior=N5–N12 (N12 dual-alone left occupancy-subtraction OPEN; N10/N11 single arms never co-dosed MB under MAOI; N5/N8/N9 ≠ MB-under-dual COX-amnestic proof)