Lobeline

Identification

Generic Name
Lobeline
DrugBank Accession Number
DB05137
Background

An alkaloid that has actions similar to nicotine on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation. [PubChem]

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 337.4553
Monoisotopic: 337.204179113
Chemical Formula
C22H27NO2
Synonyms
  • Lobelina
  • Lobeline

Pharmacology

Indication

Investigated for use/treatment in addictions.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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Pharmacodynamics

Not Available

Mechanism of action

Lobeline inhibits nicotine-evoked dopamine release and [3H]nicotine binding, thus acting as a potent antagonist at both alpha3beta2() and alpha4beta2() neuronal nicotinic receptor subtypes. However, lobeline does not release dopamine from its presynaptic terminal, but appears to induce the metabolism of dopamine intraneuronally. Reevaluation of the mechanism by which lobeline alters dopamine function reveals that its primary mechanism is inhibition of dopamine uptake and promotion of dopamine release from the storage vesicles within the presynaptic terminal, via an interaction with the tetrabenazine-binding site on the vesicular monoamine transporter (VMAT2). Thus, lobeline appears to perturb the fundamental mechanisms of dopamine storage and release. Based on its neurochemical mechanism, the ability of lobeline to functionally antagonize the neurochemical and behavioral effects of the psychostimulants amphetamine and methamphetamine was examined. Lobeline was found to inhibit the amphetamine-induced release of dopamine in vitro, and amphetamine-induced hyperactivity, drug discrimination, and self-administration.

TargetActionsOrganism
UNeuronal acetylcholine receptor subunit alpha-9Not AvailableHumans
UNeuronal acetylcholine receptor subunit alpha-10Not AvailableHumans
UNeuronal acetylcholine receptor subunit alpha-7Not 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

Adverse Effects
Adverseeffects
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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.
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Lobeline.
AmbenoniumThe risk or severity of adverse effects can be increased when Ambenonium is combined with Lobeline.
AmikacinThe therapeutic efficacy of Lobeline can be decreased when used in combination with Amikacin.
AprotininThe risk or severity of adverse effects can be increased when Aprotinin is combined with Lobeline.
AtenololThe risk or severity of adverse effects can be increased when Atenolol is combined with Lobeline.
BetaineThe risk or severity of adverse effects can be increased when Betaine is combined with Lobeline.
BetaxololThe risk or severity of adverse effects can be increased when Betaxolol is combined with Lobeline.
BisoprololThe risk or severity of adverse effects can be increased when Bisoprolol is combined with Lobeline.
CapreomycinThe therapeutic efficacy of Lobeline can be decreased when used in combination with Capreomycin.
CapsaicinThe risk or severity of adverse effects can be increased when Capsaicin is combined with Lobeline.
Interactions
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Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Alkyl-phenylketones
Alternative Parents
Benzoyl derivatives / Aryl alkyl ketones / Aralkylamines / Piperidines / Beta-amino ketones / 1,3-aminoalcohols / Trialkylamines / Secondary alcohols / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
1,3-aminoalcohol / Alcohol / Alkyl-phenylketone / Amine / Aralkylamine / Aromatic alcohol / Aromatic heteromonocyclic compound / Aryl alkyl ketone / Azacycle / Benzenoid
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amine, aromatic ketone, piperidine alkaloid (CHEBI:48723) / Piperidine alkaloids (C07475)
Affected organisms
Not Available

Chemical Identifiers

UNII
D0P25S3P81
CAS number
90-69-7
InChI Key
MXYUKLILVYORSK-HBMCJLEFSA-N
InChI
InChI=1S/C22H27NO2/c1-23-19(15-21(24)17-9-4-2-5-10-17)13-8-14-20(23)16-22(25)18-11-6-3-7-12-18/h2-7,9-12,19-21,24H,8,13-16H2,1H3/t19-,20+,21-/m0/s1
IUPAC Name
2-[(2R,6S)-6-[(2S)-2-hydroxy-2-phenylethyl]-1-methylpiperidin-2-yl]-1-phenylethan-1-one
SMILES
CN1[C@H](C[C@H](O)C2=CC=CC=C2)CCC[C@@H]1CC(=O)C1=CC=CC=C1

References

General References
  1. Miller DK, Lever JR, Rodvelt KR, Baskett JA, Will MJ, Kracke GR: Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists. Drug Alcohol Depend. 2007 Jul 10;89(2-3):282-91. Epub 2007 Mar 21. [Article]
  2. Wu J, Liu Q, Yu K, Hu J, Kuo YP, Segerberg M, St John PA, Lukas RJ: Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors. J Physiol. 2006 Oct 1;576(Pt 1):103-18. Epub 2006 Jul 6. [Article]
KEGG Drug
D02364
KEGG Compound
C07475
PubChem Compound
101616
PubChem Substance
175426951
ChemSpider
91814
BindingDB
50080818
RxNav
6464
ChEBI
48723
ChEMBL
CHEMBL122270
ZINC
ZINC000000001624
PDBe Ligand
L0B
Wikipedia
Lobeline
PDB Entries
4afh / 5afh / 5afj / 5afk / 5afl / 5afm / 5afn / 5oug / 5ouh

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Unknown StatusDiagnosticAmphetamine-Related Disorders1
1Unknown StatusTreatmentMethamphetamine Dependence2

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)130.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0298 mg/mLALOGPS
logP3.73ALOGPS
logP3.78ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.42ChemAxon
pKa (Strongest Basic)8.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity101.51 m3·mol-1ChemAxon
Polarizability39.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.942
Blood Brain Barrier+0.9382
Caco-2 permeable+0.7747
P-glycoprotein substrateSubstrate0.5231
P-glycoprotein inhibitor IInhibitor0.768
P-glycoprotein inhibitor IINon-inhibitor0.8243
Renal organic cation transporterInhibitor0.599
CYP450 2C9 substrateNon-substrate0.6908
CYP450 2D6 substrateNon-substrate0.685
CYP450 3A4 substrateSubstrate0.5086
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9062
CYP450 3A4 inhibitorNon-inhibitor0.8758
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9258
Ames testNon AMES toxic0.8059
CarcinogenicityNon-carcinogens0.9332
BiodegradationNot ready biodegradable0.8264
Rat acute toxicity2.4113 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6268
hERG inhibition (predictor II)Non-inhibitor0.5405
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00kr-2259000000-4d73b7d95ef446b7f665
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01ox-0198000000-86a5946ca7fcd847faf0

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Calcium channel activity
Specific Function
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasm...
Gene Name
CHRNA9
Uniprot ID
Q9UGM1
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-9
Molecular Weight
54806.63 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an i...
Gene Name
CHRNA10
Uniprot ID
Q9GZZ6
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-10
Molecular Weight
49704.295 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Briggs CA, McKenna DG: Activation and inhibition of the human alpha7 nicotinic acetylcholine receptor by agonists. Neuropharmacology. 1998 Sep;37(9):1095-102. [Article]

Drug created on October 21, 2007 22:23 / Updated on February 21, 2021 18:51