Evidence map›Paper›PMID 42127455›Full record

Trial reportNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026

A phase 1, safety, tolerability, and pharmacokinetics study of bisnorcymserine, a highly selective inhibitor of butyrylcholinesterase.

Iason Tzieras, Apostolos Manolopoulos, David Tweedie, Weiming Luo, Maria Maccecchini, Josephine M Egan, Nigel H Greig, Dimitrios Kapogiannis

Abstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Iason TzierasLaboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Apostolos ManolopoulosLaboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
David TweedieTranslational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Weiming LuoTranslational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Maria MaccecchiniAnnovis Bio, Inc., Malvern, PA, USA.
Josephine M EganLaboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Nigel H GreigTranslational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Dimitrios KapogiannisLaboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA. Electronic address: kapogiannisd@mail.nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholinergic deficiency is a hallmark neurotransmitter abnormality in Alzheimer's disease (AD) that has traditionally been addressed with cholinesterase inhibitors. In severe AD, butyrylcholinesterase (BuChE) becomes the dominant cholinesterase, suggesting a potential therapeutic target. (-)-N1,N8-bisnorcymserine tartrate (BNC) is a selective BuChE inhibitor designed to address this unmet need. We conducted a phase I, single-center, randomized, double-blind, placebo-controlled, ascending single oral dose clinical trial to evaluate the safety, tolerability, and pharmacokinetics of BNC in 30 healthy volunteers. There were no adverse events (AEs) grade 2 or above or any serious adverse events (SAEs). Most events were mild and self-limited, the most common being asymptomatic bradycardia and headache. The mean AUC

Indexed as

ButyrylcholinesteraseCholinesterase InhibitorsPhysostigmineAdultDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedYoung AdultButyrylcholinesteraseCholinesterase InhibitorsPhysostigmineAlzheimer’s diseaseButyrylcholinesteraseCholinesterase inhibitorClinical trialDrug safety

Identifiers

PMID42127455
PMCPMC13195608

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.