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Identification
NameGuvacine
Accession NumberDB08848
TypeSmall Molecule
GroupsExperimental
DescriptionGuvacine 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.
Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Guvacine hydrochloride
Thumb
  • InChI Key: FGNUNVVTHHKDAM-UHFFFAOYSA-N
  • Monoisotopic Mass: 163.040006276
  • Average Mass: 163.602
DBSALT000094
Categories
UNII41538P325K
CAS number498-96-4
WeightAverage: 127.1412
Monoisotopic: 127.063328537
Chemical FormulaC6H9NO2
InChI KeyQTDZOWFRBNTPQR-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
Pharmacology
IndicationThere is no approved indication for guvacine.
Structured Indications Not Available
PharmacodynamicsExperimental studies are still being investigated to determine all of the physiological effects of guvacine.
Mechanism of actionExperimental 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Sodium- and chloride-dependent GABA transporter 2Proteinunknown
inhibitor
HumanQ9NSD5 details
Sodium- and chloride-dependent GABA transporter 1Proteinunknown
inhibitor
HumanP30531 details
Sodium- and chloride-dependent GABA transporter 3Proteinunknown
inhibitor
HumanP48066 details
Sodium- and chloride-dependent betaine transporterProteinunknown
inhibitor
HumanP48065 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
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. [PubMed:10903390 ]
  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 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (39.8 KB)
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point306 - 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)3.76ChemAxon
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassNot Available
Sub ClassNot Available
Direct ParentAlkaloids and derivatives
Alternative Parents
Substituents
  • Alkaloid or derivatives
  • Guvacine
  • Tetrahydropyridine
  • Hydropyridine
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
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
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. [PubMed:458448 ]
  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. [PubMed:10903390 ]
  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. [PubMed:20512624 ]
Kind
Protein
Organism
Human
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
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. [PubMed:20512624 ]
Kind
Protein
Organism
Human
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
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. [PubMed:20512624 ]
Kind
Protein
Organism
Human
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
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. [PubMed:12111824 ]
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Drug created on March 01, 2013 18:48 / Updated on August 17, 2016 12:24