Pagoclone
Encyclopedia
Pagoclone is an anxiolytic
drug from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone
. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepine
s, which have similar effects to the older benzodiazepine
group, but with quite different chemical structure
s.
Pagoclone was originally developed as an anti-anxiety drug, but never commercialised. It is a partial agonist
acting at GABAA
receptors
in the brain. In contrast to zopiclone, pagoclone produces anxiolytic effects with little or no sedative
or amnestic actions at low doses. This is because pagoclone is a subtype-selective drug which binds primarily to the α2/α3 subtypes of the GABAA receptor which are responsible for the anti-anxiety effects of these kind of drugs, but has relatively little efficacy at the α1 subtype which produces the sedative and memory loss effects.
David Nutt
from the University of Bristol
has suggested pagoclone as a possible base from which to make a better social drug, as it produces the positive effects of alcohol
, such as relaxation and sociability, but without also causing the negative effects like aggression, amnesia
, nausea
, loss of coordination and liver damage. Its effect can be quickly reversed by the action of flumazenil
, which is already used as an antidote to benzodiazepine overdose
.
Dr. Nutt has published studies praising the potential of pagoclone which were financed by Indevus which holds the patents to the pharmaceutical and is, as of Spring 2006, seeking funding for a possible production of the compound. The significance of this is undetermined, but the long-term safety of pagoclone has not been assessed. The abuse potential of pagoclone has been assessed as being similar to, or slightly less than that of diazepam
and it would also be expected to be somewhat safer due to its relatively weaker sedative effects, but development of pagoclone as a recreational drug would still be unlikely due to concerns about abuse.
Pagoclone is also being trialed as a drug to improve a stammerer's speech fluency.http://www.stutteringstudy.comhttp://clinicaltrials.gov/ct2/show/NCT00830154
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
drug from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone
Zopiclone
Zopiclone is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the name Lunesta...
. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
s, which have similar effects to the older benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
group, but with quite different chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
s.
Pagoclone was originally developed as an anti-anxiety drug, but never commercialised. It is a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
acting at GABAA
GABA A receptor
The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
in the brain. In contrast to zopiclone, pagoclone produces anxiolytic effects with little or no sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
or amnestic actions at low doses. This is because pagoclone is a subtype-selective drug which binds primarily to the α2/α3 subtypes of the GABAA receptor which are responsible for the anti-anxiety effects of these kind of drugs, but has relatively little efficacy at the α1 subtype which produces the sedative and memory loss effects.
David Nutt
David Nutt
David John Nutt is a British psychiatrist and neuropsychopharmacologist specialising in the research of drugs that affect the brain and conditions such as addiction, anxiety and sleep. He was until 2009 a professor at the University of Bristol heading their Psychopharmacology Unit...
from the University of Bristol
University of Bristol
The University of Bristol is a public research university located in Bristol, United Kingdom. One of the so-called "red brick" universities, it received its Royal Charter in 1909, although its predecessor institution, University College, Bristol, had been in existence since 1876.The University is...
has suggested pagoclone as a possible base from which to make a better social drug, as it produces the positive effects of alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, such as relaxation and sociability, but without also causing the negative effects like aggression, amnesia
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, loss of coordination and liver damage. Its effect can be quickly reversed by the action of flumazenil
Flumazenil
Flumazenil is a benzodiazepine antagonist available for injection only, and the only benzodiazepine receptor antagonist on the market today.It was first introduced in 1987 by Hoffmann-La Roche under the trade name Anexate, but only approved by...
, which is already used as an antidote to benzodiazepine overdose
Benzodiazepine overdose
Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. Death as a result of benzodiazepines is uncommon but does occasionally happen. Deaths after hospital admission are considered to be low...
.
Dr. Nutt has published studies praising the potential of pagoclone which were financed by Indevus which holds the patents to the pharmaceutical and is, as of Spring 2006, seeking funding for a possible production of the compound. The significance of this is undetermined, but the long-term safety of pagoclone has not been assessed. The abuse potential of pagoclone has been assessed as being similar to, or slightly less than that of diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and it would also be expected to be somewhat safer due to its relatively weaker sedative effects, but development of pagoclone as a recreational drug would still be unlikely due to concerns about abuse.
Pagoclone is also being trialed as a drug to improve a stammerer's speech fluency.http://www.stutteringstudy.comhttp://clinicaltrials.gov/ct2/show/NCT00830154