Talk:Pagoclone

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Fatal overdose may occur when GABAergic substances are combined with other depressants such as opiates, benzodiazepines, barbiturates, gabapentinoids, thienodiazepines or alcohol.[1]

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

Summary sheet: Pagoclone


Template:SubstanceBox/Pagoclone


Pagoclone is a non-benzodiazepine anxiolytic of the cyclopyrrolone class., While it is closely related to "Z-drugs" (like zolpidem and zopiclone), pagoclone is unique in that it does not produce sedation or as much loss of motor control and amnesia that benzodiazepines and other Z-drugs do. As with many z-drugs, it is reported to cause hallucinations similar to deliriants, albeit with much less pronounced effects.

Pagoclone has been considered by David Nutt, in his search for alcohol alternatives, as a useful base from which to derive viable alternatives.[2] This seems to indicate Pagoclone itself is not a a viable candidate, which may be due to it's proximity to compounds with much abuse potential (e.g. benzodiazepines, z-drugs).[3]

Pagoclone was trialed as a drug to improve a stammerer's speech fluency, but research for this application was discontinued following disappointing results.[4]

Chemistry

Pagoclone is a hypnotic nonbenzodiazepine drug of the cyclopyrrolone class.

Pharmacology

Pagoclone binds with roughly equivalent high affinity (0.7–9.1 nM) to the benzodiazepine binding site of human GABAA receptors containing either an α1, α2, α3 or α5 subunit. It is a partial agonist at α1-, α2- and α5-containing GABAA receptors and a full agonist at receptors containing an α3 subunit.[5] In rats 5′-hydroxypagoclone was identified as a major metabolite. This metabolite has a considerably greater efficacy at the α1 subtype than the parent compound and was shown to have significant anxiolytic-like activity and to produce sedation.[6]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects
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Visual effects
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Cognitive effects
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Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

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Additional experience reports can be found here:

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Toxicity and harm potential

By itself, pagoclone likely has a low toxicity relative to dose. However, it is potentially lethal when mixed with depressants like benzodiazepines, alcohol or opioids.

It is strongly recommended that one use harm reduction practices when using this substance.

Tolerance and addiction potential

Pagoclone is extremely physically and psychologically addictive. This compound may have an even greater addictive potential than benzodiazepines. Tolerance will develop to the anxiolytic effects within a couple of weeks of daily use. After cessation, the tolerance returns to baseline in 7 - 14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.

Pagoclone presents cross-tolerance with all benzodiazepines, meaning that after its consumption benzodiazepines and most other GABAgenic depressants will have a reduced effect.[7]

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

Legal status

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This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • Presumably, pagoclone is illegal to produce, supply, or import under the Psychoactive Substance Act, which came into effect on May 26th, 2016.

See also

External links

References

  1. Risks of Combining Depressants - TripSit 
  2. Alcohol alternatives – a goal for psychopharmacology? D. J. Nutt https://doi.org/10.1177/0269881106063042
  3. de Wit H, Vicini L, Haig GM, Hunt T, Feltner D. Evaluation of the abuse potential of pagoclone, a partial GABAA agonist. Journal of Clinical Psychopharmacology. 2006 Jun;26(3):268-73
  4. Exploratory Randomized Clinical Study of Pagoclone in Persistent Developmental Stuttering Maguire et. al. Journal of Clinical Psychopharmacology: February 2010 - Volume 30 - Issue 1 - p 48-56 doi: 10.1097/JCP.0b013e3181caebbe
  5. The benzodiazepine binding site of GABAA receptors as a target for the development of novel anxiolytics John R Atack https://doi.org/10.1517/13543784.14.5.601
  6. The in vivo properties of pagoclone in rat are most likely mediated by 5′-hydroxy pagoclone John R. Atack et. al. https://doi.org/10.1016/j.neuropharm.2005.11.014
  7. Zopiclone and triazolam in insomnia associated with generalized anxiety disorder. If zopiclone has been taken for more than a few weeks, then the medication should be gradually reduced or preferably crossed over to an equivalent dose of diazepam (Valium) which has a much longer half-life, making withdrawal easier. One should then gradually taper the dose over a period of several months to avoid extremely severe and unpleasant withdrawal symptoms which can last up to two years after withdrawal if the withdrawal is done too abruptly. http://www.benzo.org.uk/manual/