Trial reportAnesthesiology2012
Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers.
Trial report in Anesthesiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Proposing a "Brain Health Checkup (BHC)" as a Global Potential "Standard of Care" to Overcome Reward Dysregulation in Primary Care Medicine: Coupling Genetic Risk Testing and Induction of "Dopamine Homeostasis".International journal of environmental research and public health · 2022Pooled it
- Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study.BMC anesthesiology · 2024Trial
- Efficacy and Tolerability of Oral Compared with Sublingual Ketamine Lozenges as Rescue Analgesics in Adults for Acute Pain: The OSKet Trial.Clinical drug investigation · 2021Trial
- Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers.British journal of anaesthesia · 2021Trial
- CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects.British journal of clinical pharmacology · 2015Trial
- The absolute bioavailability of racemic ketamine from a novel sublingual formulation.British journal of clinical pharmacology · 2014Trial
- Effect of ECT-anesthetics on reorientation time.European archives of psychiatry and clinical neuroscience · 2026Article
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Managing Chronic Pain: The Ketamine Option.CNS drugs · 2026Review
- Nitric Oxide Donor Sodium Nitroprusside Reduces Racemic Ketamine-But Not Esketamine-Induced Pain Relief.ACS pharmacology & translational science · 2024Article
- Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.INNOSC theranostics & pharmacological sciences · 2024Article
- Narrative Review: Low-Dose Ketamine for Pain Management.Journal of clinical medicine · 2023Review
- Application of Ketamine in Pain Management and the Underlying Mechanism.Pain research & management · 2023Review
- Midazolam Attenuates Esketamine-Induced Overactive Behaviors in Mice Before the Sedation, but Not During the Recovery.Frontiers in veterinary science · 2022Article
- Article
- Predictive performance of parent-metabolite population pharmacokinetic models of (S)-ketamine in healthy volunteers.European journal of clinical pharmacology · 2021Article
- Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy.Clinical pharmacokinetics · 2016Review
- Chronic ketamine treatment-induced changes in contractility characteristics of the mouse detrusor.International urology and nephrology · 2014Article
- Ketamine for chronic pain: risks and benefits.British journal of clinical pharmacology · 2014Review
- Translational PK-PD modeling in pain.Journal of pharmacokinetics and pharmacodynamics · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin.
methodsIn 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine-induced analgesia and cognition was quantified; the S-ketamine dosage was 20 mg/h for 2 h. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model.
resultsS-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment and reduced psychomotor speed, reaction time, and cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine- induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectively, the ketamine contribution to analgesia is -3.8 cm (visual analog pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect of -2.3 cm. The blood-effect site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min and was 6.1 min averaged across all endpoints.
conclusionsThis first observation that norketamine produces effects in the opposite direction of ketamine requires additional proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.