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Pagoclone

Pagoclone molecule structurePagoclone molecule structure
Chemical Class

Pagoclone belongs to the cyclopyrrolone class,1 structurally related to zopiclone. It reduces anxiety with little sedation or memory impairment at low doses. It was investigated as a potential treatment for panic disorder1 and stuttering2, but was never commercialized after trials showed insufficient efficacy to support continued development. Its abuse potential has been assessed as similar to, or slightly lower than, that of diazepam.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Moderate0.3-0.6 mg/day

Subjective Effects

Subjective Effects not written up yet

Pharmacology

Pharmacodynamics

Pagoclone enhances GABA-A receptor activity through the benzodiazepine binding site.3 It binds with high affinity to receptors containing α1, α2, α3, or α5 subunits, acting as a partial agonist at α1-, α2-, and α5-containing receptors and an essentially full agonist at α3-containing receptors. Its affinity for receptors containing α4 or α6 subunits is low. Human receptor-occupancy and eye-movement findings are consistent with partial agonist activity.

Pharmacokinetics

Pagoclone forms hydroxypagoclone, a primary phase I metabolite, in humans.4 This metabolite was detected after incubation with hepatocytes and liver S-9 fractions, but not liver microsomes.4 In rats, its concentrations in brain and plasma were 10-20 times those of pagoclone; higher metabolite concentrations were also reported in squirrel monkeys.

Interactions

Interactions not written up yet

An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.

Check TripSit

Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Tolerance probably develops with sufficiently prolonged use, but no general development timeframe is specified. With 0.15–0.60 mg taken every 12 hours, tolerance to learning and memory impairment was evident by day 6, when the impairments observed on day 1 were no longer apparent. Fatigue also decreased between days 1 and 65 across these doses, although complete tolerance to this effect was not established.

Harm Potential

Addiction & Dependence

Psychological

Moderate

Pagoclone's abuse potential appears similar to or slightly less than diazepam, with development concerns related to abuse.

Physical

Moderate

Physical dependence probably develops over sufficient time, with tolerance and possible withdrawal symptoms such as anxiety and insomnia.

Toxicity

central nervous system

Reported acute effects include drowsiness, impairment, sedation, and reduced learning, memory, and alertness.

History & Culture

Origins and early development

Pagoclone was synthesized by a French team working for Rhone-Poulenc & Rorer S.A. A 1994 Rhone-Poulenc patent described the compound and its proposed therapeutic properties. Rhone-Poulenc subsequently licensed it to the American company Interneuron Pharmaceuticals, which later became…

Legality

By Country

Illegal1
United Kingdom flagUnited KingdomIllegal (analog/blanket ban)
Controlled / restricted1
Australia flagAustraliaRestricted
Not scheduled2
United States flagUnited StatesNot scheduled
Canada flagCanadaNot scheduled

References

Citations

  1. Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder. Journal of Psychopharmacology (2001). https://doi.org/10.1177/02698811010150031212
  2. The Pharmacologic Treatment of Stuttering and Its Neuropharmacologic Basis. Frontiers in Neuroscience (2020). https://doi.org/10.3389/fnins.2020.001581
  3. The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy pagoclone. ResearchGate, reproducing the Neuropharmacology abstract (2006). https://doi.org/10.1016/j.neuropharm.2005.11.0141
  4. Assessment of a Micropatterned Hepatocyte Coculture System to Generate Major Human Excretory and Circulating Drug Metabolites. Drug Metabolism and Disposition (2010). https://doi.org/10.1124/dmd.110.03487612
  5. Preliminary effects of pagoclone, a partial GABAA agonist, on neuropsychological performance. Neuropsychiatric Disease and Treatment (2008). https://doi.org/10.2147/ndt.s23511
  6. Indevus Pharmaceuticals, Inc. — 2002 Form 10-K. U.S. Securities and Exchange Commission (2002). https://www.sec.gov/Archives/edgar/data/854222/000092701602006055/d10k.htm12345
  7. Pagoclone and Clinical Trials. Stuttering Foundation (2006). https://www.stutteringhelp.org/pagoclone-and-clinical-trials12
  8. Indevus Pharmaceuticals — 2006 Form 10-K. AnnualReports (2006). https://www.annualreports.com/HostedData/AnnualReports/PDF/INDEVUSPHARMACE10K.pdf1234
  9. Endo Pharmaceuticals Holdings Inc. — March 2009 Form 10-Q. U.S. Securities and Exchange Commission (2009). https://www.sec.gov/Archives/edgar/data/1100962/000119312509107336/d10q.htm1
  10. Indevus Announces Agreement with Teva to Develop Pagoclone for the Treatment of Stuttering. U.S. Securities and Exchange Commission (2008). https://www.sec.gov/Archives/edgar/data/854222/000119312508203939/dex991.htm123

Article Status

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