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
- Weight
- Average: 337.4553
Monoisotopic: 337.204179113 - Chemical Formula
- C22H27NO2
- Synonyms
- Lobelina
- Lobeline
Pharmacology
- Indication
Investigated for use/treatment in addictions.
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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.
Target Actions Organism UNeuronal acetylcholine receptor subunit alpha-7 Not Available Humans UNeuronal acetylcholine receptor subunit alpha-9 Not Available Humans UNeuronal acetylcholine receptor subunit alpha-10 Not Available 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 outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Lobeline. Ambenonium The risk or severity of adverse effects can be increased when Ambenonium is combined with Lobeline. Amikacin The therapeutic efficacy of Lobeline can be decreased when used in combination with Amikacin. Aprotinin The risk or severity of adverse effects can be increased when Aprotinin is combined with Lobeline. Atenolol The risk or severity of adverse effects can be increased when Atenolol is combined with Lobeline. - 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
- 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]
- 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]
- External Links
- PDB Entries
- 4afh / 5afh / 5afj / 5afk / 5afl / 5afm / 5afn / 5oug / 5ouh
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Unknown Status Diagnostic Amphetamine-Related Disorders 1 1 Unknown Status Treatment Methamphetamine Dependence 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 130.5 °C PhysProp - Predicted Properties
Property Value Source Water Solubility 0.0298 mg/mL ALOGPS logP 3.73 ALOGPS logP 3.78 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 14.43 Chemaxon pKa (Strongest Basic) 8.77 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 40.54 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 101.51 m3·mol-1 Chemaxon Polarizability 39.27 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.942 Blood Brain Barrier + 0.9382 Caco-2 permeable + 0.7747 P-glycoprotein substrate Substrate 0.5231 P-glycoprotein inhibitor I Inhibitor 0.768 P-glycoprotein inhibitor II Non-inhibitor 0.8243 Renal organic cation transporter Inhibitor 0.599 CYP450 2C9 substrate Non-substrate 0.6908 CYP450 2D6 substrate Non-substrate 0.685 CYP450 3A4 substrate Substrate 0.5086 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9062 CYP450 3A4 inhibitor Non-inhibitor 0.8758 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9258 Ames test Non AMES toxic 0.8059 Carcinogenicity Non-carcinogens 0.9332 Biodegradation Not ready biodegradable 0.8264 Rat acute toxicity 2.4113 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6268 hERG inhibition (predictor II) Non-inhibitor 0.5405
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 195.967472 predictedDarkChem Lite v0.1.0 [M-H]- 196.696972 predictedDarkChem Lite v0.1.0 [M-H]- 179.2903 predictedDeepCCS 1.0 (2019) [M+H]+ 195.831472 predictedDarkChem Lite v0.1.0 [M+H]+ 197.070572 predictedDarkChem Lite v0.1.0 [M+H]+ 181.64832 predictedDeepCCS 1.0 (2019) [M+Na]+ 195.742472 predictedDarkChem Lite v0.1.0 [M+Na]+ 196.849872 predictedDarkChem Lite v0.1.0 [M+Na]+ 188.69316 predictedDeepCCS 1.0 (2019)
Targets
- 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
- Briggs CA, McKenna DG: Activation and inhibition of the human alpha7 nicotinic acetylcholine receptor by agonists. Neuropharmacology. 1998 Sep;37(9):1095-102. [Article]
- 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
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51