Identification

Name
Clenbuterol
Accession Number
DB01407
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-Clenbuterol
  • (±)-clenbuterol
  • 1-(4-Amino-3,5-dichloro-phenyl)-2-tert-butylamino-ethanol
  • 4-amino-3,5-Dichloro-alpha-(((1,1-dimethylethyl)amino)methyl)benzenemethanol
  • 4-amino-alpha-((Tert-butylamino)methyl)-3,5-dichlorobenzyl alcohol
  • 4-amino-α-((tert-butylamino)methyl)-3,5-dichlorobenzyl alcohol
  • CLENBUTEROL
  • Clenbuterolum
Product Ingredients
IngredientUNIICASInChI Key
Clenbuterol hydrochlorideGOR5747GWU21898-19-1OPXKTCUYRHXSBK-UHFFFAOYSA-N
International/Other Brands
Monores (Valeas) / Spiropent (Boehringer Ingelheim)
Categories
UNII
XTZ6AXU7KN
CAS number
37148-27-9
Weight
Average: 277.19
Monoisotopic: 276.079618622
Chemical Formula
C12H18Cl2N2O
InChI Key
STJMRWALKKWQGH-UHFFFAOYSA-N
InChI
InChI=1S/C12H18Cl2N2O/c1-12(2,3)16-6-10(17)7-4-8(13)11(15)9(14)5-7/h4-5,10,16-17H,6,15H2,1-3H3
IUPAC Name
1-(4-amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethan-1-ol
SMILES
CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1

Pharmacology

Indication

Used as a bronchodilator in the treatment of asthma patients.

Pharmacodynamics

Clenbuterol is a substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. Although approved for use in some countries, as of fall, 2006, clenbuterol is not an ingredient of any therapeutic drug approved by the U.S. Food and Drug Administration.

Mechanism of action

Clenbuterol is a Beta(2) agonist similar in some structural respects to salbutamol. Agonism of the beta(2) receptor stimulates adenylyl cyclase activity which ultimately leads to downstream effects of smooth muscle relaxation in the bronchioles.

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
UBeta-1 adrenergic receptor
agonist
Human
UBeta-3 adrenergic receptor
agonist
Human
UBeta-nerve growth factor
stimulator
Human
UTumor necrosis factor
other/unknown
Human
Absorption

89-98% orally

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

36-39 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Clenbuterol.
AbirateroneThe serum concentration of Clenbuterol can be increased when it is combined with Abiraterone.
AcebutololThe therapeutic efficacy of Clenbuterol can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Clenbuterol.
AlclometasoneThe risk or severity of hypokalemia can be increased when Alclometasone is combined with Clenbuterol.
AlfuzosinThe therapeutic efficacy of Clenbuterol can be decreased when used in combination with Alfuzosin.
AlprenololAlprenolol may decrease the bronchodilatory activities of Clenbuterol.
AmcinonideThe risk or severity of hypokalemia can be increased when Amcinonide is combined with Clenbuterol.
AmineptineThe risk or severity of adverse effects can be increased when Amineptine is combined with Clenbuterol.
AmitriptylineThe therapeutic efficacy of Clenbuterol can be decreased when used in combination with Amitriptyline.
Food Interactions
Not Available

References

Synthesis Reference

Keck, J., Kruger, G., Machleidt, H., Noll, K., Engelhardt, G. and Eckenfels, A.; U S . Patent 3,536,712; October 27,1970: assigned to Boehringer lngelheim G.m.b.H. (Germany).

General References
Not Available
External Links
Human Metabolome Database
HMDB0015477
PubChem Compound
2783
PubChem Substance
46508373
ChemSpider
2681
BindingDB
27958
ChEBI
174690
ChEMBL
CHEMBL49080
Therapeutic Targets Database
DAP000945
PharmGKB
PA164745640
Wikipedia
Clenbuterol
ATC Codes
R03AC14 — ClenbuterolR03CC13 — Clenbuterol
MSDS
Download (73.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentCongestive Cardiomyopathy / Heart Failure, Unspecified1
1, 2CompletedTreatmentPompe's Disease1
Not AvailableRecruitingBasic ScienceMuscle Hypertrophy in Healthy Young Men1

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)174-175.5Keck, J., Kruger, G., Machleidt, H., Noll, K., Engelhardt, G. and Eckenfels, A.; U S . Patent 3,536,712; October 27,1970: assigned to Boehringer lngelheim G.m.b.H. (Germany).
Predicted Properties
PropertyValueSource
Water Solubility0.112 mg/mLALOGPS
logP2.94ALOGPS
logP2.33ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)14.06ChemAxon
pKa (Strongest Basic)9.63ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area58.28 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity73.38 m3·mol-1ChemAxon
Polarizability28.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9484
Blood Brain Barrier+0.8631
Caco-2 permeable+0.5375
P-glycoprotein substrateSubstrate0.5588
P-glycoprotein inhibitor INon-inhibitor0.8863
P-glycoprotein inhibitor IINon-inhibitor0.9627
Renal organic cation transporterNon-inhibitor0.9052
CYP450 2C9 substrateNon-substrate0.8142
CYP450 2D6 substrateNon-substrate0.683
CYP450 3A4 substrateNon-substrate0.5835
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5428
Ames testNon AMES toxic0.8858
CarcinogenicityNon-carcinogens0.5199
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6024 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9704
hERG inhibition (predictor II)Non-inhibitor0.8546
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-MSNot Available
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/MSsplash10-0zfr-0690000000-4ea9999e9adf3d869e7d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0pb9-0090000000-4787e85eeb46d25e48eb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-9081f080310110b928b2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0uyi-0970000000-180db1557f9de0905570
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-0900000000-5607a3961d5b1b526aca
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-0900000000-f99c3fbb74f4657c8588
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0900000000-1b8353b766cd0eb328a2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f8c-1900000000-b34f6b0fe72dbe12dc7b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0zgl-4900000000-85c1e6d67f6eb7f4660c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-9600000000-6d5ae5d64081ef26b128

Taxonomy

Description
This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
Aniline and substituted anilines / Aralkylamines / Aryl chlorides / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Primary amines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
show 1 more
Substituents
1,3-dichlorobenzene / Aniline or substituted anilines / Aralkylamine / Aryl chloride / Aryl halide / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Hydrocarbon derivative
show 12 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
substituted aniline, secondary amino compound, dichlorobenzene, primary arylamine, ethanolamines, amino alcohol (CHEBI:174690)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Zhu Y, Culmsee C, Roth-Eichhorn S, Krieglstein J: Beta(2)-adrenoceptor stimulation enhances latent transforming growth factor-beta-binding protein-1 and transforming growth factor-beta1 expression in rat hippocampus after transient forebrain ischemia. Neuroscience. 2001;107(4):593-602. [PubMed:11720783]
  2. Ryall JG, Gregorevic P, Plant DR, Sillence MN, Lynch GS: Beta 2-agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol. Am J Physiol Regul Integr Comp Physiol. 2002 Dec;283(6):R1386-94. Epub 2002 Sep 5. [PubMed:12388476]
  3. Choo JJ, Horan MA, Little RA, Rothwell NJ: Anabolic effects of clenbuterol on skeletal muscle are mediated by beta 2-adrenoceptor activation. Am J Physiol. 1992 Jul;263(1 Pt 1):E50-6. [PubMed:1322047]
  4. Sillence MN, Matthews ML, Spiers WG, Pegg GG, Lindsay DB: Effects of clenbuterol, ICI118551 and sotalol on the growth of cardiac and skeletal muscle and on beta 2-adrenoceptor density in female rats. Naunyn Schmiedebergs Arch Pharmacol. 1991 Oct;344(4):449-53. [PubMed:1685013]
  5. Mazzanti G, Di Sotto A, Daniele C, Battinelli L, Brambilla G, Fiori M, Loizzo S, Loizzo A: A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model. Food Chem Toxicol. 2007 Sep;45(9):1694-9. Epub 2007 Mar 12. [PubMed:17449161]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Baker JG: The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. 2010 Jul;160(5):1048-61. doi: 10.1111/j.1476-5381.2010.00754.x. [PubMed:20590599]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Baker JG: The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. 2010 Jul;160(5):1048-61. doi: 10.1111/j.1476-5381.2010.00754.x. [PubMed:20590599]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Stimulator
General Function
Receptor signaling protein activity
Specific Function
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signal...
Gene Name
NGF
Uniprot ID
P01138
Uniprot Name
Beta-nerve growth factor
Molecular Weight
26958.53 Da
References
  1. Culmsee C, Semkova I, Krieglstein J: NGF mediates the neuroprotective effect of the beta2-adrenoceptor agonist clenbuterol in vitro and in vivo: evidence from an NGF-antisense study. Neurochem Int. 1999 Jul;35(1):47-57. [PubMed:10403429]
  2. Semkova I, Krieglstein J: Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Brain Res Rev. 1999 Aug;30(2):176-88. [PubMed:10525174]
  3. Puls I, Beck M, Giess R, Magnus T, Ochs G, Toyka KV: [Clenbuterol in amyotrophic lateral sclerosis. No indication for a positive effect]. Nervenarzt. 1999 Dec;70(12):1112-5. [PubMed:10637819]
  4. Samina Riaz S, Tomlinson DR: Pharmacological modulation of nerve growth factor synthesis: a mechanistic comparison of vitamin D receptor and beta(2)-adrenoceptor agonists. Brain Res Mol Brain Res. 2000 Dec 28;85(1-2):179-88. [PubMed:11146120]
  5. Riaz SS, Tomlinson DR: Clenbuterol stimulates neurotrophic support in streptozotocin-diabetic rats. Diabetes Obes Metab. 1999 Jan;1(1):43-51. [PubMed:11221812]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
References
  1. Izeboud CA, Mocking JA, Monshouwer M, van Miert AS, Witkamp RF: Participation of beta-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release. J Recept Signal Transduct Res. 1999 Jan-Jul;19(1-4):191-202. [PubMed:10071758]
  2. Yoshimura T: [Modulation of cytokine production from human mononuclear cells by several agents]. Yakugaku Zasshi. 2000 Dec;120(12):1277-90. [PubMed:11193379]
  3. Izeboud CA, Hoebe KH, Grootendorst AF, Nijmeijer SM, van Miert AS, Witkamp RR, Rodenburg RJ: Endotoxin-induced liver damage in rats is minimized by beta 2-adrenoceptor stimulation. Inflamm Res. 2004 Mar;53(3):93-9. Epub 2004 Feb 16. [PubMed:15021963]
  4. Laan TT, Bull S, Pirie RS, Fink-Gremmels J: Evaluation of cytokine production by equine alveolar macrophages exposed to lipopolysaccharide, Aspergillus fumigatus, and a suspension of hay dust. Am J Vet Res. 2005 Sep;66(9):1584-9. [PubMed:16261833]
  5. van den Hoven R, Duvigneau JC, Hartl RT, Gemeiner M: Clenbuterol affects the expression of messenger RNA for interleukin 10 in peripheral leukocytes from horses challenged intrabronchially with lipopolysaccharides. Vet Res Commun. 2006 Nov;30(8):921-8. [PubMed:17139543]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on July 17, 2007 06:33 / Updated on October 01, 2018 16:41