ArticleBritish journal of pharmacology2018
Pharmacology in translation: the preclinical and early clinical profile of the novel α2/3 functionally selective GABA
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04592536 (A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject), which is not on this map. Cited by 30 papers.
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.
A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject
Who cites it
30 citing papers in PubMed.
- Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the α2/3/5-Subtype Selective GABAClinical pharmacology in drug development · 2021Trial
- Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABABritish journal of anaesthesia · 2019Trial
- Direct modulation of human GABA-A αFrontiers in neuroscience · 2026Review
- Article
- Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.Journal of psychopharmacology (Oxford, England) · 2024Article
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Established and emerging GABAFrontiers in pharmacology · 2024Review
- SLIC-Occ: functional segmentation of occupancy images improves precision of ECEJNMMI physics · 2023Article
- Pharmaco-EEG analysis of ligands varying in selectivity for α1 subunit-containing GABAPsychopharmacology · 2023Article
- New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.CNS drugs · 2023Review
- The pyridazine heterocycle in molecular recognition and drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
- From mechanisms to markers: novel noninvasive EEG proxy markers of the neural excitation and inhibition system in humans.Translational psychiatry · 2022Review
- Pronounced antiseizure activity of the subtype-selective GABACNS neuroscience & therapeutics · 2022Article
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- multi-patient dose synthesis of [18F]Flumazenil via a copper-mediatedEJNMMI radiopharmacy and chemistry · 2022Article
- ECEuropean journal of nuclear medicine and molecular imaging · 2022Article
- Emerging technologies and their impact on regulatory science.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- A local-neighborhood Lassen plot filter for creating occupancy and non-displaceable binding images.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Article
- Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits.International journal of molecular sciences · 2021Review
Corrections and comments
- Commented on bySpinal GABA2019
- Erratum issuedCorrection.2019
Authors and funding
23 authors.
Funding
Abstract
background and purposeBenzodiazepines, non-selective positive allosteric modulators (PAMs) of GABA EXPERIMENTAL APPROACH: In vitro screening assays were used to identify molecules with functional selectivity for receptors containing α2/3 subunits over those containing α1 subunits. In vivo receptor occupancy (RO) was conducted, prior to confirmation of in vivo α2/3 and α1 pharmacology through quantitative EEG (qEEG) beta frequency and zolpidem drug discrimination in rats respectively. PF-06372865 was then progressed to Phase 1 clinical trials. KEY
resultsPF-06372865 exhibited functional selectivity for those receptors containing α2/3/5 subunits, with significant positive allosteric modulation (90-140%) but negligible activity (≤20%) at GABA CONCLUSIONS AND IMPLICATIONS: PF-06372865 has a unique clinical pharmacology profile and a highly predictive translational data package from preclinical species to the clinical setting.
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.