Details of the Drug

General Information of Drug (ID: DMSREPX)

• Drug Name: Levobetaxolol
• Synonyms: Levobetaxolol [INN]; Betaxon (TN); (2S)-1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(propan-2-ylamino)propan-2-ol; (2S)-1-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-3-(propan-2-ylamino)propan-2-ol; (2s)-1-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-3-(isopropylamino)propan-2-ol; (S)-(-)-Betaxolol; (S)-1-(isopropylamino)-3-[p-(cyclopropylmethoxyethyl)phenoxy]-2-propanol; (S)-Betaxolol

Indication

Disease Entry	ICD 11	Status	REF
Chronic open-angle glaucoma	9C61.0	Approved	[1]

• Therapeutic Class: Cardiotonic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 307.4
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3 h [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 20 hours [2]
• Chemical Identifiers:
  Formula: C18H29NO3
  IUPAC Name: (2S)-1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(propan-2-ylamino)propan-2-ol
  Canonical SMILES: CC(C)NC[C@@H](COC1=CC=C(C=C1)CCOCC2CC2)O
  InChI: InChI=1S/C18H29NO3/c1-14(2)19-11-17(20)13-22-18-7-5-15(6-8-18)9-10-21-12-16-3-4-16/h5-8,14,16-17,19-20H,3-4,9-13H2,1-2H3/t17-/m0/s1
  InChIKey: NWIUTZDMDHAVTP-KRWDZBQOSA-N
• Cross-matching ID:
  PubChem CID: 60657
  ChEBI ID: CHEBI:59254
  CAS Number: 93221-48-8
  DrugBank ID: DB09351
  TTD ID: D0A6CQ
  INTEDE ID: DR0932

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Levobetaxolol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Atracurium	DM42HXN	Moderate	Additive neuromuscular blocking effects by the combination of Levobetaxolol and Atracurium.	Corneal disease [9A76-9A78]	[23]
Siponimod	DM2R86O	Major	Increased risk of bradycardia by the combination of Levobetaxolol and Siponimod.	Multiple sclerosis [8A40]	[24]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Levobetaxolol and Ozanimod.	Multiple sclerosis [8A40]	[25]

References

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• [2] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [3] Binding affinities of ocular hypotensive beta-blockers levobetaxolol, levobunolol, and timolol at endogenous guinea pig beta-adrenoceptors. J Ocul Pharmacol Ther. 2004 Apr;20(2):93-9.
• [4] Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432.
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• [6] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [7] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [8] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [9] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [10] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [11] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [12] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [13] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [14] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [15] Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
• [16] Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G269-77.
• [17] Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999 Feb;27(2):325-31.
• [18] Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6.
• [19] Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension. Drugs Aging. 2006;23(12):977-95.
• [20] Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
• [21] beta-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):519-29.
• [22] beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25.
• [23] Harrah MD, Way WL, Katzung BG "The interaction of d-tubocurarine with antiarrhythmic drugs." Anesthesiology 33 (1970): 406-10. [PMID: 5512329]
• [24] Cerner Multum, Inc. "Australian Product Information.".
• [25] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.