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The Promises and Pitfalls of Reboxetine

2003· review· en· W2047492413 on OpenAlexaboutno aff
Michelle E. Page

Bibliographic record

VenueCNS Drug Reviews · 2003
Typereview
Languageen
FieldNeuroscience
TopicNeurotransmitter Receptor Influence on Behavior
Canadian institutionsnot available
Fundersnot available
KeywordsReboxetinePharmacologyAntidepressantDesipramineReuptakeNorepinephrine transporterReuptake inhibitorTricyclicMedicineNorepinephrineInternal medicineReceptorDopamineSerotoninHippocampus

Abstract

fetched live from OpenAlex

The antidepressant compound, morpholine, 2-[(2-ethoxyphenoxy)phenylmethyl]-,methanesulfonate, or reboxetine, is a selective noradrenergic reuptake inhibitor that acts by binding to the norepinephrine (NE) transporter and blocking reuptake of extracellular NE back into terminals. This compound has low affinity for other transporters and receptors. The development of reboxetine as a potential antidepressant stems from the prior demonstration that blockade of the NE transporter imparts antidepressant activity. Desipramine, lofepramine, and nortryptiline are examples of tricyclic antidepressant (TCA) compounds from the first generation of antidepressants that exert their effects by blockade of NE reuptake. Maprotiline, a non-tricyclic compound, is also a NE selective reuptake inhibitor. Unfortunately, these antidepressants are also associated with interactions with muscarinic, histaminergic, and adrenergic receptors, which are known to contribute to a variety of untoward side effects. Despite the positive pharmacological profile of reboxetine, i.e., selectivity and specificity, with relatively fewer side effects, its use as an antidepressant is currently limited to Europe. Reboxetine is marketed as Edronax in the UK, Norebox in Italy, and as Irenor in Spain. It is registered in Germany, Sweden, Denmark, Ireland, Austria and Finland. Based on studies conducted primarily outside the US, the FDA granted a preliminary letter of approval in 1999. However, more recent clinical studies conducted in the US and Canada, prompted by the FDA, resulted in a letter of non-approval. To date, it is unclear why the further development of reboxetine as an antidepressant in the US has been halted. Despite this setback, reboxetine has been a valuable pharmacological tool to assess the role of the noradrenergic system in preclinical studies of depressive disorder.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.009
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.009
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0090.012
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0010.003
Scholarly communication0.0030.006
Open science0.0010.002
Research integrity0.0040.008
Insufficient payload (model declined to judge)0.0080.003

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.120
GPT teacher head0.373
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations38
Published2003
Admission routes1
Has abstractyes

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