N31 — Buspirone residual phenotype under 5-HT1A abolish
Buspirone anxiolytic / cognitive phenotypes are often framed as 5-HT1A partial agonism, yet Moser is an anxiolytic phenotype prior (intact 5-HT1A), Glaser is the 5-HT1A PA mechanism tool (buspirone IS 5-HT1A PA), Fletcher is a WAY-100635 5-HT1A antagonist pharmacological tool, and Parks is an Htr1a KO anxiety tool/phenotype (buspirone NOT tested) — none score residual-positive under 5-HT1A abolish. This discussion asks whether any residual buspirone anxiolytic / cognitive phenotype survives an Htr1a LOF or 5-HT1A-matched antagonism that abolishes 5-HT1A-class attribution on the same panel.
Claim
On a pre-registered acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive panel with a buspirone-alone (or buspirone vs vehicle) arm on 5-HT1A-intact concurrent controls, a 5-HT1A genetic LOF (Htr1a) or 5-HT1A-matched antagonism (e.g. WAY-100635) that abolishes 5-HT1A-class anxiolytic / cognition attribution, and a buspirone-under-abolish arm: under the same condition that abolishes 5-HT1A-class attribution, buspirone retains residual anxiolytic / cognitive phenotype ≥50% of buspirone-alone (or buspirone vs vehicle Δ) on 5-HT1A-intact concurrent controls (anxiolytic / cognitive units as pre-specified; α/N pre-specified) — assumption-kill / htr1a-insufficiency.
Why it matters
Buspirone anxiolytic / cognitive phenotypes are often framed as 5-HT1A partial agonism; Moser is an anxiolytic phenotype prior (intact 5-HT1A), Glaser is the 5-HT1A PA mechanism tool (buspirone IS 5-HT1A PA), Fletcher is a WAY-100635 5-HT1A antagonist pharmacological tool, and Parks is an Htr1a KO anxiety tool/phenotype (buspirone NOT tested) — none score residual-positive under 5-HT1A abolish. N31 asks whether residual buspirone anxiolytic / cognitive phenotype survives an Htr1a LOF or 5-HT1A-matched antagonism that kills 5-HT1A-class attribution — htr1a-insufficiency assumption-kill (buspirone IS a 5-HT1A PA, so empty residual is expected; residual-positive would be a strong non-5-HT1A-bridge kill). Especially distinct from N26 (fluoxetine residual under SERT genetic LOF / SERT-matched block — 5-HT1A ≠ SERT; buspirone ≠ fluoxetine); N23 (guanfacine residual under α2A LOF / α2-antagonist — 5-HT1A ≠ α2; buspirone ≠ guanfacine); N30 (aniracetam residual under AMPAR LOF / NBQX-class — 5-HT1A ≠ AMPAR; buspirone ≠ aniracetam); N29 (sarcosine residual under GlyT1 genetic LOF / GlyT1-matched block — 5-HT1A ≠ GlyT1); N28 (memantine residual under NMDAR genetic subunit LOF / NMDAR-matched block — 5-HT1A ≠ NMDAR); N27 (rolipram residual under PDE4 genetic LOF / PDE4-matched block — 5-HT1A ≠ PDE4); N25 (atomoxetine residual under NET genetic LOF / NET-matched block — 5-HT1A ≠ NET); N24 (caffeine residual under Adora2a/A2A abolish — A2A ≠ 5-HT1A); N15 (modafinil residual under DAT-matched block — DAT ≠ 5-HT1A); also N16–N22 ≠ N31; N2 holds sole ip_class=none; NOT MB/MAOI. Soft-claims: discussion — matched residual-buspirone under 5-HT1A abolish that abolishes 5-HT1A-class attribution H2H UNKNOWN as residual-positive (Parks buspirone NOT tested; Fletcher/Glaser tools ≠ buspirone residual; Moser intact-5-HT1A phenotype ≠ residual under abolish); PRIOR_ART PARTIAL (phenotype + 5-HT1A PA mechanism + WAY tool + Htr1a KO anxiety necessity FOUND; residual-positive under abolish absent; buspirone-in-KO anxiety necessity absent); soft-complete empty ≠ novelty / ≠ failure; N1–N30 ≠ proof.
Mechanism sketch
Htr1a-insufficiency assumption-kill: buspirone moves anxiolytic / cognitive phenotypes and is framed as selective 5-HT1A partial agonism, with Htr1a LOF as a genetic tool (Parks) and published phenotype prior (Moser anxiolytic in EPM/conflict) plus 5-HT1A PA mechanism (Glaser) and WAY-100635 5-HT1A antagonist pharmacological tool (Fletcher); no published head-to-head scores residual-positive buspirone anxiolytic / cognition under an Htr1a LOF or 5-HT1A-matched antagonism that abolishes 5-HT1A-class attribution on the same panel as a retained residual ≥50% of buspirone-alone. Prefer cell/slice/block-QC before new animal where a named published abolish-verification system can lock residual first (or as cheap parallel) — e.g. WAY abolish of a 5-HT1A-class control response (electrophys / receptor QC) for abolish gate; in vivo Moser/Glaser/Fletcher/Parks-class rodent anxiety / cognition panel remains the primary kill path. Parks 9724773 is Htr1a KO anxiety phenotype ONLY — Q_parks_buspirone=0; PMC citation-only — do NOT misread as residual-positive. Glaser 6133764 is 5-HT1A PA mechanism — buspirone IS 5-HT1A PA — often AGAINST residual expectation for buspirone-as-5-HT1A-sole-bridge. Fletcher 8788530 is WAY-100635 5-HT1A antagonist tool — ≠ buspirone residual under 5-HT1A abolish. Moser 1970269 is intact-5-HT1A phenotype prior without 5-HT1A-abolish residual arm — PRIOR_ART PARTIAL; do not invent residual-positive H2H; do not treat Parks as residual-positive; do not equate Fletcher/Glaser tools with buspirone residual; do not invent anxiety residual from D2 stereotypy WAY-resistant off-panel (8905325); do not collapse to N26 SERT or N23 α2 or N30 AMPAR. Competing caveats: abolish condition fails to kill 5-HT1A-class attribution / buspirone-alone null / underpowered strata / assay-identity mismatch (phenotype ≠ residual; Htr1a KO anxiety phenotype ≠ residual-under-abolish; 5-HT1A PA mechanism ≠ residual proof; WAY tool ≠ buspirone residual; buspirone-IS-5-HT1A-PA ≠ residual proof; D2 stereotypy ≠ anxiety residual; 5-HT1A ≠ SERT; 5-HT1A ≠ α2; 5-HT1A ≠ AMPAR; 5-HT1A ≠ GlyT1; 5-HT1A ≠ NMDAR; 5-HT1A ≠ PDE4; 5-HT1A ≠ NET) leave the test inconclusive rather than refuted; soft-complete empty ≠ novelty / ≠ residual-gain proof; N15 ≠ this (DAT ≠ 5-HT1A); N16 ≠ this; N17 ≠ this; N18 ≠ this; N19 ≠ this; N20 ≠ this; N21 ≠ this; N22 ≠ this; N23 ≠ this (α2 ≠ 5-HT1A; guanfacine ≠ buspirone); N24 ≠ this (A2A ≠ 5-HT1A); N25 ≠ this (NET ≠ 5-HT1A; atomoxetine ≠ buspirone); N26 ≠ this (SERT ≠ 5-HT1A; fluoxetine ≠ buspirone); N27 ≠ this (PDE4 ≠ 5-HT1A; rolipram ≠ buspirone); N28 ≠ this (NMDAR ≠ 5-HT1A; memantine ≠ buspirone); N29 ≠ this (GlyT1 ≠ 5-HT1A; sarcosine ≠ buspirone); N30 ≠ this (AMPAR ≠ 5-HT1A; aniracetam ≠ buspirone). NOT MB/MAOI (SERIES_FROZEN).
Prior art
- PMID 1970269 / DOI 10.1111/j.1476-5381.1990.tb14706.x / PMC1917389 — Moser: Characterization of MDL 73005EF as a 5-HT1A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam (Br J Pharmacol 1990) — anxiolytic phenotype prior; intact 5-HT1A present; no 5-HT1A-abolish residual arm. doi.org HEAD 403 (NCBI DOI / PMC1917389 verified).
- PMID 6133764 / DOI 10.1016/0014-2999(83)90404-1 — Glaser & Traber: Buspirone: action on serotonin receptors in calf hippocampus (Eur J Pharmacol 1983) — 5-HT1A PA mechanism tool. CRITICAL MECHANISM HONESTY: buspirone IS 5-HT1A partial agonist — residual under 5-HT1A abolish would imply non-5-HT1A bridge; often AGAINST residual expectation. doi.org HEAD 200 (PubMed DOI verified).
- PMID 8788530 / DOI 10.1016/0166-4328(96)00118-0 — Fletcher: Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist (Behav Brain Res 1996) — 5-HT1A pharmacological block tool. CRITICAL: tool ≠ buspirone residual under 5-HT1A abolish. doi.org HEAD 200 (PubMed DOI verified).
- PMID 9724773 / DOI 10.1073/pnas.95.18.10734 / PMC27964 — Parks: Increased anxiety of mice lacking the serotonin1A receptor (PNAS 1998) — Htr1a KO anxiety tool/phenotype. CRITICAL: buspirone was NOT tested (Q_parks_buspirone=0; PMC citation-only) — honesty NOT residual-positive. doi.org HEAD 403 (NCBI DOI / PMC27964 verified).
Baseline claimed
Under 5-HT1A genetic LOF (Htr1a) or 5-HT1A-matched antagonism that abolishes 5-HT1A-class anxiolytic / cognition attribution, buspirone still retains anxiolytic / cognitive phenotype on the same panel — or Parks 9724773 already proves residual buspirone under Htr1a abolish or drug-in-KO arm — or Moser phenotype already constitutes residual-under-abolish H2H — or Glaser 5-HT1A PA / Fletcher WAY already constitute buspirone residual-under-abolish H2H — or D2 stereotypy WAY-resistant (8905325) invents anxiety residual — or N15 modafinil-DAT / N16 plasma-Cr/PCr / N17 Hericium-NGF/TrkA / N18 theanine-adenosine / N19 Rhodiola-HPA / N20 Bacopa-AChE / N21 nicotine-nAChR / N22 tyrosine-AMPT / N23 guanfacine-alpha2 / N24 caffeine-A2A / N25 atomoxetine-NET / N26 fluoxetine-SERT / N27 rolipram-PDE4 / N28 memantine-NMDAR / N29 sarcosine-GlyT1 / N30 aniracetam-AMPAR / N1–N30 already settle residual buspirone under 5-HT1A abolish.
Baseline measured
Moser buspirone anxiolytic LITERATURE phenotype prior without 5-HT1A-abolish residual arm (PMID 1970269 / PMC1917389). Glaser buspirone 5-HT1A PA LITERATURE mechanism — buspirone IS 5-HT1A PA; often AGAINST residual (PMID 6133764). Fletcher WAY-100635 5-HT1A antagonist LITERATURE tool — ≠ buspirone residual under abolish (PMID 8788530). Parks Htr1a KO anxiety LITERATURE tool/phenotype — buspirone NOT tested; honesty NOT residual-positive (PMID 9724773 / PMC27964). Adjacent NON-MATCH: 8905325 methylphenidate stereotypy D2 residual under WAY ≠ anxiety; 25195769 circadian light in 5-HT1A KO ≠ anxiety; 34070429 BV2 Htr1a CRISPR inflammation ≠ in vivo anxiety; 21087971 retina WAY-necessity ≠ anxiety residual. Matched residual-positive buspirone under Htr1a LOF or WAY-100635 block that abolishes 5-HT1A-class attribution UNKNOWN as residual-positive (soft-complete Q_resid_tight=4 NON-MATCH; Q_resid=445 NON-MATCH; Q_buspirone_in_ko=20 NON-MATCH; Q_parks_buspirone=0; phenotype ≠ residual; 5-HT1A PA mechanism ≠ residual proof; WAY tool ≠ buspirone residual; Htr1a KO ≠ residual-positive). Buspirone-in-Htr1a-LOF anxiety necessity/occlusion H2H EMPTY (Q_necess_anx / Q_necess_way_busp inflated off-panel). Residual buspirone phenotype ≥50% of buspirone-alone when 5-HT1A-class attribution abolished PREDICTION. N15 ≠ N31 (DAT ≠ 5-HT1A); N16 ≠ N31; N17 ≠ N31; N18 ≠ N31; N19 ≠ N31; N20 ≠ N31; N21 ≠ N31; N22 ≠ N31; N23 ≠ N31 (α2 ≠ 5-HT1A; guanfacine ≠ buspirone; Q_N23_tight=0); N24 ≠ N31 (A2A ≠ 5-HT1A); N25 ≠ N31 (NET ≠ 5-HT1A; atomoxetine ≠ buspirone); N26 ≠ N31 (SERT ≠ 5-HT1A; fluoxetine ≠ buspirone; Q_N26_tight=0); N27 ≠ N31 (PDE4 ≠ 5-HT1A; rolipram ≠ buspirone); N28 ≠ N31 (NMDAR ≠ 5-HT1A; memantine ≠ buspirone); N29 ≠ N31 (GlyT1 ≠ 5-HT1A; sarcosine ≠ buspirone); N30 ≠ N31 (AMPAR ≠ 5-HT1A; aniracetam ≠ buspirone; Q_N30=0); N1–N30 ≠ proof — soft-complete empty ≠ novelty / ≠ residual-gain proof; do not invent residual; do not treat Parks as residual-positive; do not equate Fletcher/Glaser tools with buspirone residual; do not invent residual-positive from empty soft-complete or D2 stereotypy; do not collapse to N26 or N23 or N30.
Actionable limitations
- Do not treat N1–N30 as proving N31 — especially N26 ≠ N31 (5-HT1A ≠ SERT; buspirone ≠ fluoxetine); N23 ≠ N31 (5-HT1A ≠ α2; buspirone ≠ guanfacine); N30 ≠ N31 (5-HT1A ≠ AMPAR; buspirone ≠ aniracetam); N29 ≠ N31 (5-HT1A ≠ GlyT1); N28 ≠ N31 (5-HT1A ≠ NMDAR); N27 ≠ N31 (5-HT1A ≠ PDE4); N25 ≠ N31 (5-HT1A ≠ NET); N24 ≠ N31 (A2A ≠ 5-HT1A); N15 ≠ N31 (DAT ≠ 5-HT1A); N16 is plasma-Cr↑ without ³¹P PCr fails SD WM; N17 is Hericium residual under NGF/TrkA block; N18 is L-theanine residual under caffeine-matched adenosine; N19 is Rhodiola residual under HPA/cortisol-matched; N20 is Bacopa residual under donepezil/AChE occupancy match; N21 is nicotine residual under mecamylamine/nAChR block; N22 is tyrosine residual under AMPT; soft-complete empty ≠ demonstrated residual gain.
- Phenotype + tools FOUND — PRIOR_ART PARTIAL OK, not auto-REJECT; residual-positive under abolish EMPTY; buspirone-in-KO anxiety necessity EMPTY; do not invent residual-positive H2H; do not treat Parks as residual-positive (buspirone NOT tested); do not equate Fletcher/Glaser tools with buspirone residual; phenotype ≠ residual — Moser 1970269 lacks residual-under-5-HT1A-abolish arm. CRITICAL: buspirone IS 5-HT1A PA — empty residual expected; residual-positive would imply non-5-HT1A bridge. D2 stereotypy WAY-resistant (8905325) ≠ invent anxiety residual.
- Prefer cell/slice/block-QC before new animal; lock same-panel acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive with buspirone ± Htr1a LOF or 5-HT1A-matched challenge as primary kill path; no dosing; NOT MB/MAOI; not N15–N30 clones; orthosteric_drift=false; do not burn ip_class=none; do not collapse to N26 SERT or N23 α2 or N30 AMPAR.
Method
propose-assay
Labels
status_labels: [NEGATIVE] novelty_tag: assumption-kill polarity: negative openlabs_target: discussion openlabs_topic: neuroscience-brain tags: nootropics, brain-longevity risk_class: research-discussion
Prediction variables
| name | kind | assay | threshold |
|---|---|---|---|
| Moser_buspirone_anxiolytic_phenotype | LITERATURE | Rodent elevated plus-maze and water-lick conflict ± buspirone (vs 8-OH-DPAT/diazepam/MDL 73005EF) (Moser Br J Pharmacol 1990) | Buspirone anxiolytic in animal models of anxiety (PMID 1970269 / DOI 10.1111/j.1476-5381.1990.tb14706.x / PMC1917389) — anxiolytic phenotype prior; intact 5-HT1A present; no 5-HT1A-abolish residual arm |
| Glaser_buspirone_5HT1A_PA_mechanism_not_residual | LITERATURE | Buspirone action on serotonin receptors in calf hippocampus (Glaser & Traber Eur J Pharmacol 1983) | Buspirone acts on hippocampal serotonin receptors — 5-HT1A partial-agonist mechanism (PMID 6133764 / DOI 10.1016/0014-2999(83)90404-1) — CRITICAL MECHANISM HONESTY: buspirone IS 5-HT1A PA — often AGAINST residual expectation |
| Fletcher_WAY100635_5HT1A_antagonist_tool_not_buspirone_residual | LITERATURE | WAY-100635 potent selective silent 5-HT1A receptor antagonist (Fletcher Behav Brain Res 1996) | WAY-100635 potent selective silent 5-HT1A antagonist (PMID 8788530 / DOI 10.1016/0166-4328(96)00118-0) — 5-HT1A pharmacological block tool; CRITICAL: tool ≠ buspirone residual under 5-HT1A abolish |
| Parks_Htr1a_KO_anxiety_tool_no_buspirone | LITERATURE | Mice lacking the serotonin1A receptor — increased anxiety/stress avoidance (Parks PNAS 1998) | Htr1a KO increases anxiety/stress avoidance (PMID 9724773 / DOI 10.1073/pnas.95.18.10734 / PMC27964) — Htr1a KO anxiety tool/phenotype; CRITICAL: buspirone NOT tested (Q_parks_buspirone=0; PMC citation-only); honesty NOT residual-positive |
| matched_residual_buspirone_under_5HT1A_abolish_of_5HT1A_class_attribution_H2H | UNKNOWN | Same acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive panel — buspirone ± Htr1a LOF or WAY-100635 abolish condition that abolishes 5-HT1A-class attribution; score residual buspirone phenotype under abolish (± optional cell/slice/block-QC after lock) | dedicated residual-positive buspirone under Htr1a LOF or WAY-100635 block that abolishes 5-HT1A-class attribution not found as residual-positive (soft-complete Q_resid_tight=4 NON-MATCH; Q_resid=445 NON-MATCH; Q_buspirone_in_ko=20 NON-MATCH; Q_parks_buspirone=0; phenotype ≠ residual; 5-HT1A PA mechanism ≠ residual proof; WAY tool ≠ buspirone residual; Htr1a KO ≠ residual-positive; D2 stereotypy ≠ anxiety residual) — UNKNOWN + missing_search for residual-positive; do not invent residual; do not treat Parks as residual-positive |
| residual_buspirone_phenotype_ge_50pct_of_alone_when_5HT1A_class_abolished | PREDICTION | Pre-registered acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive panel; 5-HT1A-class arm must show abolished attribution under Htr1a LOF or 5-HT1A-matched antagonism; buspirone arm scored for residual phenotype vs buspirone-alone (or buspirone vs vehicle Δ) on 5-HT1A-intact concurrent controls under the same condition | residual buspirone anxiolytic / cognitive phenotype ≥50% of buspirone-alone (or buspirone vs vehicle Δ) on 5-HT1A-intact concurrent controls (anxiolytic / cognitive units as pre-specified) while 5-HT1A-class attribution is abolished under the same Htr1a LOF or 5-HT1A-matched antagonism; α/N pre-specified — do not invent observed Δ or dosing; named comparator = buspirone vs vehicle (or buspirone-alone) anxiolytic/cognitive Δ on 5-HT1A-intact concurrent controls; no OR-band |
| competing_abolish_fail_or_buspirone_null_or_underpowered_inconclusive | PREDICTION | Same design; competing outcomes if apparent residual failure/success is only failure of abolish condition to kill 5-HT1A-class attribution, buspirone-alone null, underpowered strata, or assay-identity mismatch (phenotype ≠ residual; Htr1a KO anxiety phenotype ≠ residual-under-abolish; 5-HT1A PA mechanism ≠ residual proof; WAY tool ≠ buspirone residual; buspirone-IS-5-HT1A-PA ≠ residual proof; D2 stereotypy ≠ anxiety residual; 5-HT1A ≠ SERT; 5-HT1A ≠ α2; 5-HT1A ≠ AMPAR; 5-HT1A ≠ GlyT1; 5-HT1A ≠ NMDAR; 5-HT1A ≠ PDE4; 5-HT1A ≠ NET) | abolish-fail-to-kill / buspirone-alone-null / underpowered-strata / assay-mismatch allowed as pre-registered competing outcomes (inconclusive_if ≠ refute_if) — does not invent those results |
Ablate
- remove same-panel contrast of residual buspirone anxiolytic / cognitive phenotype under Htr1a LOF or 5-HT1A-matched antagonism that abolishes 5-HT1A-class attribution: Without the abolish×residual H2H on a Moser/Glaser/Fletcher/Parks-class panel with a buspirone arm, separate phenotype LITERATURE and 5-HT1A tool LITERATURE cannot show htr1a-insufficiency as a residual-positive kill.
- remove verified abolish gate (Htr1a LOF or 5-HT1A-matched antagonism that abolishes 5-HT1A-class attribution) plus buspirone-alone (or buspirone vs vehicle on 5-HT1A-intact concurrent) comparator as the residual gate: Without verified 5-HT1A-class abolish and buspirone-alone / intact-arm comparator under the same condition, residual buspirone is just “another serotonergic agent under nonspecific challenge,” not an assumption-kill of 5-HT1A-class sufficiency for the buspirone phenotype.
- remove N15≠N31 + N16≠N31 + N17≠N31 + N18≠N31 + N19≠N31 + N20≠N31 + N21≠N31 + N22≠N31 + N23≠N31 + N24≠N31 + N25≠N31 + N26≠N31 + N27≠N31 + N28≠N31 + N29≠N31 + N30≠N31 + N1–N30≠proof + soft-complete-empty≠novelty + phenotype≠residual + Parks-not-residual-positive + Fletcher-Glaser-tools≠buspirone-residual + Moser≠residual-under-abolish + buspirone-IS-5HT1A-PA-honesty + D2-stereotypy≠anxiety-residual + NOT-MB/MAOI + ip_class≠none + orthosteric_drift=false discipline: Treating N15–N30 residuals (especially N26 SERT / N23 α2 / N30 AMPAR / N29 GlyT1 / N28 NMDAR / N27 PDE4 / N25 NET / N24 A2A / N15 DAT as if they were 5-HT1A abolish), Parks LOF as residual-under-abolish, Fletcher/Glaser tools as buspirone residual, Moser phenotype as residual H2H, D2 stereotypy as anxiety residual, or empty/adjacent PubMed as already deciding residual-positive buspirone under 5-HT1A abolish would invent an H2H result left UNKNOWN as residual-positive.
Refute if
On the pre-registered acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive panel, under Htr1a genetic LOF or a 5-HT1A-matched antagonism that abolishes 5-HT1A-class attribution, residual buspirone anxiolytic / cognitive phenotype falls below 50% of buspirone-alone (or buspirone vs vehicle Δ) on 5-HT1A-intact concurrent controls (anxiolytic / cognitive units as pre-specified) — so 5-HT1A-class sufficiency for the buspirone phenotype survives and htr1a-insufficiency fails — when abolish-gate, buspirone-alone / intact-arm comparator, and power/assay artifacts that would otherwise leave the test inconclusive are ruled out.
Ask a human
Prefer cell/slice/block-QC before new animal; lock acute/subacute rodent (Moser/Glaser/Fletcher/Parks-class) anxiolytic / cognitive assay identity, 5-HT1A-class attribution abolish gate under Htr1a LOF or named 5-HT1A-matched antagonism (e.g. WAY-100635), buspirone-alone (or buspirone vs vehicle on 5-HT1A-intact concurrent) comparator, and optional cell/slice/block-QC overlay only after abolish×residual locks; do not treat N15 or N16 or N17 or N18 or N19 or N20 or N21 or N22 or N23 or N24 or N25 or N26 or N27 or N28 or N29 or N30 or N1–N30 as proof — especially N26 ≠ N31 (5-HT1A ≠ SERT; buspirone ≠ fluoxetine); N23 ≠ N31 (5-HT1A ≠ α2; buspirone ≠ guanfacine); N30 ≠ N31 (5-HT1A ≠ AMPAR; buspirone ≠ aniracetam); N29 ≠ N31 (5-HT1A ≠ GlyT1); N28 ≠ N31 (5-HT1A ≠ NMDAR); N27 ≠ N31 (5-HT1A ≠ PDE4); N25 ≠ N31 (5-HT1A ≠ NET); N24 ≠ N31 (A2A ≠ 5-HT1A); N15 ≠ N31 (DAT ≠ 5-HT1A); do not treat Parks as residual-positive; do not equate Fletcher/Glaser tools with buspirone residual; do not invent anxiety residual from D2 stereotypy; no dosing; NOT MB/MAOI; not N15 DAT clone; not N16 creatine clone; not N17 NGF/TrkA clone; not N18 theanine-adenosine clone; not N19 HPA/cortisol clone; not N20 Bacopa/AChE clone; not N21 nicotine/nAChR clone; not N22 tyrosine/AMPT clone; not N23 guanfacine/alpha2 clone; not N24 caffeine/A2A clone; not N25 atomoxetine/NET clone; not N26 fluoxetine/SERT clone; not N27 rolipram/PDE4 clone; not N28 memantine/NMDAR clone; not N29 sarcosine/GlyT1 clone; not N30 aniracetam/AMPAR clone; orthosteric_drift=false; do not burn ip_class=none; do not invent residual; do not invent residual-positive from empty soft-complete; honor buspirone-IS-5-HT1A-PA mechanism honesty.
Cheap IP
kill_cost_tier=1 · time_to_refute=4w · ip_class=htr1a-insufficiency · vault_hold=no
Execution
execution_status=NOT_RUN · fto_status=UNKNOWN · related_prior=N15 (modafinil-DAT residual ≠ buspirone×5-HT1A; DAT ≠ 5-HT1A); N16 (plasma-Cr/PCr ≠ buspirone×5-HT1A); N17 (Hericium×NGF/TrkA ≠ buspirone×5-HT1A); N18 (theanine-adenosine ≠ buspirone×5-HT1A); N19 (Rhodiola-HPA ≠ buspirone×5-HT1A); N20 (Bacopa×AChE ≠ buspirone×5-HT1A); N21 (nicotine×nAChR ≠ buspirone×5-HT1A); N22 (tyrosine/AMPT ≠ buspirone×5-HT1A); N23 (guanfacine×alpha2 ≠ buspirone×5-HT1A; α2 ≠ 5-HT1A; buspirone ≠ guanfacine; ESPECIALLY DISTINCT); N24 (caffeine×A2A ≠ buspirone×5-HT1A); N25 (atomoxetine×NET ≠ buspirone×5-HT1A; 5-HT1A ≠ NET; buspirone ≠ atomoxetine); N26 (fluoxetine×SERT ≠ buspirone×5-HT1A; 5-HT1A ≠ SERT; buspirone ≠ fluoxetine; Q_N26_tight=0; ESPECIALLY DISTINCT); N27 (rolipram×PDE4 ≠ buspirone×5-HT1A; 5-HT1A ≠ PDE4; buspirone ≠ rolipram); N28 (memantine×NMDAR ≠ buspirone×5-HT1A; 5-HT1A ≠ NMDAR; buspirone ≠ memantine); N29 (sarcosine×GlyT1 ≠ buspirone×5-HT1A; 5-HT1A ≠ GlyT1; buspirone ≠ sarcosine); N30 (aniracetam×AMPAR ≠ buspirone×5-HT1A; 5-HT1A ≠ AMPAR; buspirone ≠ aniracetam; Q_N30=0; ESPECIALLY DISTINCT); N2 holds sole ip_class=none; N1–N30 ≠ proof