Pagoclone

Identification

Name
Pagoclone
Accession Number
DB04903
Type
Small Molecule
Groups
Investigational
Description

Pagoclone is an anxiolytic drug from the cyclopyrrolone family, which is related to other more well known drugs such as the sleeping medication zopiclone. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with quite different chemical structures.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
38VAG2SA33
CAS number
133737-32-3
Weight
Average: 407.893
Monoisotopic: 407.14005467
Chemical Formula
C23H22ClN3O2
InChI Key
HIUPRQPBWVEQJJ-UHFFFAOYSA-N
InChI
InChI=1S/C23H22ClN3O2/c1-14(2)7-10-16(28)13-19-17-5-3-4-6-18(17)23(29)27(19)21-12-9-15-8-11-20(24)25-22(15)26-21/h3-6,8-9,11-12,14,19H,7,10,13H2,1-2H3
IUPAC Name
2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-2,3-dihydro-1H-isoindol-1-one
SMILES
CC(C)CCC(=O)CC1N(C(=O)C2=CC=CC=C12)C1=NC2=C(C=CC(Cl)=N2)C=C1

Pharmacology

Indication

For the potential treatment of panic and anxiety disorders.

Pharmacodynamics

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.

Mechanism of action

Pagoclone is a subtype-selective drug which binds primarily to the alpha2/alpha3 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 alpha1 subtype which produces the sedative and memory loss effects.

TargetActionsOrganism
UGamma-aminobutyric acid receptor subunit alpha-2Not AvailableHumans
UGamma-aminobutyric acid receptor subunit alpha-3Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Pagoclone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Pagoclone.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Pagoclone.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Pagoclone is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Pagoclone.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Pagoclone is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Pagoclone.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Pagoclone.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Pagoclone.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Pagoclone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. de Wit H, Vicini L, Haig GM, Hunt T, Feltner D: Evaluation of the abuse potential of pagoclone, a partial GABAA agonist. J Clin Psychopharmacol. 2006 Jun;26(3):268-73. [PubMed:16702891]
  2. Atack JR, Pike A, Marshall G, Stanley J, Lincoln R, Cook SM, Lewis RT, Blackaby WP, Goodacre SC, McKernan RM, Dawson GR, Wafford KA, Reynolds DS: The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy pagoclone. Neuropharmacology. 2006 May;50(6):677-89. Epub 2006 Jan 20. [PubMed:16430927]
  3. Bateson A: Pagoclone Indevus. Curr Opin Investig Drugs. 2003 Jan;4(1):91-5. [PubMed:12625036]
  4. Sandford JJ, Forshall S, Bell C, Argyropoulos S, Rich A, D'Orlando KJ, Gammans RE, Nutt DJ: Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder. J Psychopharmacol. 2001 Sep;15(3):205-8. [PubMed:11565630]
External Links
PubChem Compound
131664
PubChem Substance
175426895
ChemSpider
116335
ChEMBL
CHEMBL2104745
Wikipedia
Pagoclone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentPersistent Developmental Stuttering2
2CompletedTreatmentPremature Ejaculation1
2, 3CompletedTreatmentStuttering1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00655 mg/mLALOGPS
logP4.6ALOGPS
logP5.35ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)13.39ChemAxon
pKa (Strongest Basic)-2.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area63.16 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.16 m3·mol-1ChemAxon
Polarizability44.23 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9678
Caco-2 permeable+0.5426
P-glycoprotein substrateNon-substrate0.5956
P-glycoprotein inhibitor IInhibitor0.8644
P-glycoprotein inhibitor IIInhibitor0.9725
Renal organic cation transporterNon-inhibitor0.6472
CYP450 2C9 substrateNon-substrate0.6975
CYP450 2D6 substrateNon-substrate0.7898
CYP450 3A4 substrateSubstrate0.7806
CYP450 1A2 substrateNon-inhibitor0.5159
CYP450 2C9 inhibitorNon-inhibitor0.5787
CYP450 2D6 inhibitorNon-inhibitor0.7857
CYP450 2C19 inhibitorNon-inhibitor0.5737
CYP450 3A4 inhibitorNon-inhibitor0.8476
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7115
Ames testNon AMES toxic0.6879
CarcinogenicityNon-carcinogens0.8244
BiodegradationNot ready biodegradable0.9922
Rat acute toxicity2.3601 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9273
hERG inhibition (predictor II)Non-inhibitor0.5166
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthyridines. These are compounds containing a naphthyridine moiety, a naphthalene in which a carbon atom has been replaced by a nitrogen in each of the two rings. The naphthyridine skeleton can also be described as an assembly two fused pyridine rings, which do not share their nitrogen atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Naphthyridines
Direct Parent
Naphthyridines
Alternative Parents
Isoindolones / Isoindoles / 2-halopyridines / Aryl chlorides / Benzenoids / Imidolactams / Tertiary carboxylic acid amides / Heteroaromatic compounds / Lactams / Ketones
show 6 more
Substituents
Isoindolone / Naphthyridine / Isoindoline / Isoindole / Isoindole or derivatives / 2-halopyridine / Aryl chloride / Aryl halide / Imidolactam / Benzenoid
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
Molecular Weight
51325.85 Da
References
  1. Atack JR, Pike A, Marshall G, Stanley J, Lincoln R, Cook SM, Lewis RT, Blackaby WP, Goodacre SC, McKernan RM, Dawson GR, Wafford KA, Reynolds DS: The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy pagoclone. Neuropharmacology. 2006 May;50(6):677-89. Epub 2006 Jan 20. [PubMed:16430927]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA3
Uniprot ID
P34903
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-3
Molecular Weight
55164.055 Da
References
  1. Atack JR, Pike A, Marshall G, Stanley J, Lincoln R, Cook SM, Lewis RT, Blackaby WP, Goodacre SC, McKernan RM, Dawson GR, Wafford KA, Reynolds DS: The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy pagoclone. Neuropharmacology. 2006 May;50(6):677-89. Epub 2006 Jan 20. [PubMed:16430927]

Drug created on October 21, 2007 16:23 / Updated on March 01, 2020 19:29

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