NAV

Guvacine

Identification

Generic Name
Guvacine
DrugBank Accession Number
DB08848
Background

Guvacine is a pyridine alkaloid found in the Areca nut (also known as the Betel nut). It is an experimental drug with no approved indication. Experimental studies are still being investigated to determine all of the physiological effects and mechanisms of action of guvacine. Currently it has been determined that guvacine is a specific GABA reuptake inhibitor with no significant affinity at GABA receptors.

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 127.1412
Monoisotopic: 127.063328537
Chemical Formula
C6H9NO2
Synonyms
Not Available
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

There is no approved indication for guvacine.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Experimental studies are still being investigated to determine all of the physiological effects of guvacine.

Mechanism of action

Experimental studies are still being investigated to determine the exact mechanisms of action of guvacine. What is known is that guvacine binds selectively to presynaptic GABA reuptake transporters and prevents the reuptake of GABA, but has no affinity for GABA postsynaptic receptors.

TargetActionsOrganism
USodium- and chloride-dependent GABA transporter 2
inhibitor
Humans
USodium- and chloride-dependent GABA transporter 1
inhibitor
Humans
USodium- and chloride-dependent GABA transporter 3
inhibitor
Humans
USodium- and chloride-dependent betaine transporter
inhibitor
Humans
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

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

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.
Not Available
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Guvacine hydrochlorideNot AvailableNot AvailableFGNUNVVTHHKDAM-UHFFFAOYSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Not Available
Sub Class
Not Available
Direct Parent
Alkaloids and derivatives
Alternative Parents
Hydropyridines / Amino acids / Monocarboxylic acids and derivatives / Dialkylamines / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aliphatic heteromonocyclic compound / Alkaloid or derivatives / Amine / Amino acid / Amino acid or derivatives / Azacycle / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Hydrocarbon derivative
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
secondary amino compound, alpha,beta-unsaturated monocarboxylic acid, beta-amino acid, tetrahydropyridine, pyridine alkaloid (CHEBI:5576) / Pyridine alkaloids (C10149)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
41538P325K
CAS number
498-96-4
InChI Key
QTDZOWFRBNTPQR-UHFFFAOYSA-N
InChI
InChI=1S/C6H9NO2/c8-6(9)5-2-1-3-7-4-5/h2,7H,1,3-4H2,(H,8,9)
IUPAC Name
1,2,5,6-tetrahydropyridine-3-carboxylic acid
SMILES
OC(=O)C1=CCCNC1

References

Synthesis Reference

McELVAIN SM, STORK G: Piperidine derivatives; the preparation of l-benzoyl-3-carbethoxy-4-piperidone; a synthesis of guvacine. J Am Chem Soc. 1946 Jun;68:1049-53.

General References
  1. Krogsgaard-Larsen P, Frolund B, Frydenvang K: GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects. Curr Pharm Des. 2000 Aug;6(12):1193-209. [Article]
  2. O'Neil, Maryadele J. (2013). The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals (15th ed.). Royal Society of Chemistry, The. [ISBN:978-1849736701]
KEGG Compound
C10149
PubChem Compound
3532
PubChem Substance
175427121
ChemSpider
3412
BindingDB
90787
ChEBI
5576
ChEMBL
CHEMBL76768
ZINC
ZINC000003872753
Wikipedia
Guvacine
MSDS
Download (39.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)306 - 309 °CFrom MSDS.
water solubilitySoluble in water, and almost insoluble in 100% alcohol, ether, chloroform, and benzene.From The Merck Index monographs.
Predicted Properties
PropertyValueSource
Water Solubility30.8 mg/mLALOGPS
logP-2.2ALOGPS
logP-2.6Chemaxon
logS-0.62ALOGPS
pKa (Strongest Acidic)3.57Chemaxon
pKa (Strongest Basic)9.77Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area49.33 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity33.8 m3·mol-1Chemaxon
Polarizability12.85 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9325
Blood Brain Barrier+0.5447
Caco-2 permeable-0.5696
P-glycoprotein substrateSubstrate0.6572
P-glycoprotein inhibitor INon-inhibitor0.9704
P-glycoprotein inhibitor IINon-inhibitor0.9782
Renal organic cation transporterNon-inhibitor0.6481
CYP450 2C9 substrateNon-substrate0.8893
CYP450 2D6 substrateNon-substrate0.8182
CYP450 3A4 substrateNon-substrate0.7338
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.958
CYP450 2C19 inhibitorNon-inhibitor0.9114
CYP450 3A4 inhibitorNon-inhibitor0.9888
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9907
Ames testNon AMES toxic0.8368
CarcinogenicityNon-carcinogens0.9492
BiodegradationReady biodegradable0.9306
Rat acute toxicity1.9903 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Non-inhibitor0.9056
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0560-9200000000-d8c5ef9e7cf51eb4bd41
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01t9-0900000000-fec9fb797ff02855ad37
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-2900000000-ff9f318ae43e5692ff86
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fsi-9200000000-4574d78feb81075666ee
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-576721b99bea03f3a59c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uyi-9000000000-20dcc5ec330432512744
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-84c3b604d7146ae71be7
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-123.5721275
predicted
DarkChem Lite v0.1.0
[M-H]-123.645905
predicted
DeepCCS 1.0 (2019)
[M+H]+124.2751275
predicted
DarkChem Lite v0.1.0
[M+H]+126.383514
predicted
DeepCCS 1.0 (2019)
[M+Na]+123.9271275
predicted
DarkChem Lite v0.1.0
[M+Na]+135.15416
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Sodium- and chloride-dependent GABA transporter 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Sodium-dependent GABA and taurine transporter. In presynaptic terminals, regulates GABA signaling termination through GABA uptake. May also be involved in beta-alanine transport.
Gene Name
SLC6A13
Uniprot ID
Q9NSD5
Uniprot Name
Sodium- and chloride-dependent GABA transporter 2
Molecular Weight
68008.205 Da
References
  1. Schousboe A, Thorbek P, Hertz L, Krogsgaard-Larsen P: Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding. J Neurochem. 1979 Jul;33(1):181-9. [Article]
  2. Krogsgaard-Larsen P, Frolund B, Frydenvang K: GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects. Curr Pharm Des. 2000 Aug;6(12):1193-209. [Article]
  3. Sunol C, Babot Z, Cristofol R, Sonnewald U, Waagepetersen HS, Schousboe A: A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochem Res. 2010 Sep;35(9):1384-90. doi: 10.1007/s11064-010-0196-1. Epub 2010 May 30. [Article]
Details2. Sodium- and chloride-dependent GABA transporter 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A1
Uniprot ID
P30531
Uniprot Name
Sodium- and chloride-dependent GABA transporter 1
Molecular Weight
67073.0 Da
References
  1. Sunol C, Babot Z, Cristofol R, Sonnewald U, Waagepetersen HS, Schousboe A: A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochem Res. 2010 Sep;35(9):1384-90. doi: 10.1007/s11064-010-0196-1. Epub 2010 May 30. [Article]
Details3. Sodium- and chloride-dependent GABA transporter 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A11
Uniprot ID
P48066
Uniprot Name
Sodium- and chloride-dependent GABA transporter 3
Molecular Weight
70605.145 Da
References
  1. Sunol C, Babot Z, Cristofol R, Sonnewald U, Waagepetersen HS, Schousboe A: A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochem Res. 2010 Sep;35(9):1384-90. doi: 10.1007/s11064-010-0196-1. Epub 2010 May 30. [Article]
Details4. Sodium- and chloride-dependent betaine transporter
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Transports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.
Gene Name
SLC6A12
Uniprot ID
P48065
Uniprot Name
Sodium- and chloride-dependent betaine transporter
Molecular Weight
69367.655 Da
References
  1. Ruiz-Tachiquin ME, Sanchez-Lemus E, Soria-Jasso LE, Arias-Montano JA, Ortega A: Gamma-aminobutyric acid transporter (BGT-1) expressed in human astrocytoma U373 MG cells: pharmacological and molecular characterization and phorbol ester-induced inhibition. J Neurosci Res. 2002 Jul 1;69(1):125-32. [Article]

Drug created at March 02, 2013 01:48 / Updated at April 09, 2024 18:22