NAV

Moxisylyte

Identification

Generic Name
Moxisylyte
DrugBank Accession Number
DB09205
Background

Moxisylyte, denominated as thymoxamine in the UK, is a specific and orally active α1-adrenergic antagonist.10 According to the WHO, moxisylyte is approved since 19879 and in the same year, it acquired the denomination of orphan product by the FDA.11 This drug was developed by the Japanese company Fujirebio and also by the American company Iolab in the late 80s.

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 279.38
Monoisotopic: 279.183443669
Chemical Formula
C16H25NO3
Synonyms
  • Moxisylyte
  • Thymoxamine
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

By the WHO, moxisylyte is indicated for the symptomatic management of sequelae of cerebral infarction or hemorrhage.9 The cerebral infarction is characterized by the blockage of the artery either by the formation of a thrombus or an embolus.3

On the other hand, the FDA classified moxisylyte for the reversal of phenylephrine-induced mydriasis in patients who have narrow anterior angles and are at risk of developing an acute attack of angle-closure glaucoma.11 Closed-angle glaucoma is caused by the contact between the iris and the trabecular meshwork. This contact will damage the aqueous outflow by the meshwork thus, increasing eye pressure and producing the symptoms of glaucoma.4 Mydriasis is referred to the dilatation of the pupils and this standard body function is known to be a trigger factor for the development of acute closed-angle glaucoma.This risk is explained by the generation of a pupillary block, which is the contact between the pupillary margins and the lens, thus preventing flow from the aqueous humor to the anterior chamber and followed by an increased pressure gradient.12

Moxisylyte is also approved in France as the first drug for the treatment of impotence.5

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Administration of moxisylyte has shown to improve peripheral flow in occlusive arterial disease with little effect in blood pressure. There are reports of increases in cutaneous blood flow and skin temperature after local application of moxisylyte.10

Mechanism of action

Moxisylyte is vasodilator that works as a specific alpha-adrenergic blocking agent. Its action is known to be competitive against norepinephrine without beta-receptor blocking, anti-angiotensin or anti-serotonin activity.1

TargetActionsOrganism
AAlpha adrenergic receptor
antagonist
Humans
Absorption

Moxisylyte is rapidly absorbed after oral administration.13 Its pharmacokinetic profile is linear in the dose range from 10 to 30 mg for the values of Cmax and AUC.5 After intravenous administration, the maximal plasma concentration was of 352.8 ng/ml with an AUC of 152.6 mcg h/L.8 In preclinical trials, the bioavailability was always presented in approximately 10%.14

Volume of distribution

In preclinical trials, the volume of distribution presented for beagle dogs is in the range of 0.83-0.98 L/kg.14

Protein binding

Not Available

Metabolism

The pharmacokinetic profile of moxisylyte can make this drug to be considered as a prodrug as its biotransformation is very rapid. This drug gets rapidly hydrolyzed by pseudocholinesterase in plasma and tissues to give the major metabolite deacetyl-thymoxamine.5,14 This first metabolite is later demethylated by the cytochrome P450 monooxygenase system to form deacetyl-demethyl-thymoxamine.14 Both of this major metabolites are pharmacologically active. The pharmacokinetic studies with moxisylyte in urine and feces have shown the presence of 8 different metabolites, where two of them are highly polar and resistant to enzymatic hydrolysis. From this metabolites, it has been detected the sulfate and glucuronide conjugates of the major metabolites.2,5

Hover over products below to view reaction partners

Route of elimination

The major elimination route of moxisylyte is via the kidneys.13 The complete elimination of all the metabolites by urine is of 75% when administered intravenously and 69% when administered orally.7 From the elimination profile, The specific ranges of the two major metabolites of moxisylyte in the urine are of 50% and 10% for desacetyl-thymoxamine and N-monodemethyl-desacetyl-thymoxamine respectively.6 The fecal elimination corresponded only to the 14% of the administered dose.14

Half-life

The half-life of moxisylyte was of 1-2 hours.13

Clearance

In preclinical trials, the plasma clearance was of 7.17 ml min/kg for beagle dogs.14

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Moxisylyte is very well accepted by the patients and it presents very few adverse effects. The side effects are usually related to a profound alpha blockade than to a toxic response.10

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
AbacavirAbacavir may decrease the excretion rate of Moxisylyte which could result in a higher serum level.
AcebutololMoxisylyte may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Aceclofenac is combined with Moxisylyte.
AcemetacinThe risk or severity of hypertension can be increased when Moxisylyte is combined with Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Moxisylyte which could result in a higher serum level.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Moxisylyte hydrochlorideWK2KZM9V6X964-52-3Not applicable
International/Other Brands
Carlytene

Categories

ATC Codes
C04AX10 — MoxisylyteG04BE06 — Moxisylyte
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aromatic monoterpenoids. These are monoterpenoids containing at least one aromatic ring.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Monoterpenoids
Direct Parent
Aromatic monoterpenoids
Alternative Parents
Monocyclic monoterpenoids / Phenol esters / Cumenes / Phenylpropanes / Phenoxy compounds / Phenol ethers / Toluenes / Alkyl aryl ethers / Trialkylamines / Carboxylic acid esters
show 6 more
Substituents
Alkyl aryl ether / Amine / Amino acid or derivatives / Aromatic homomonocyclic compound / Aromatic monoterpenoid / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cumene
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
PW8QYA7KI0
CAS number
54-32-0
InChI Key
VRYMTAVOXVTQEF-UHFFFAOYSA-N
InChI
InChI=1S/C16H25NO3/c1-11(2)14-10-15(20-13(4)18)12(3)9-16(14)19-8-7-17(5)6/h9-11H,7-8H2,1-6H3
IUPAC Name
4-[2-(dimethylamino)ethoxy]-2-methyl-5-(propan-2-yl)phenyl acetate
SMILES
CC(C)C1=C(OCCN(C)C)C=C(C)C(OC(C)=O)=C1

References

General References
  1. Wand M, Grant WM: Thymoxamine hydrochloride: an alpha-adrenergic blocker. Surv Ophthalmol. 1980 Sep-Oct;25(2):75-84. [Article]
  2. Duchene P, Bernouillet C, Bromet-Petit M, Mosser J, Feniou C, Gaudin D, Virelizier H: Metabolism of 14C-thymoxamine in rat and man. Xenobiotica. 1988 Aug;18(8):919-28. doi: 10.3109/00498258809167515. [Article]
  3. Samad F, Ruf W: Inflammation, obesity, and thrombosis. Blood. 2013 Nov 14;122(20):3415-22. doi: 10.1182/blood-2013-05-427708. Epub 2013 Oct 3. [Article]
  4. Pandit RJ, Taylor R: Mydriasis and glaucoma: exploding the myth. A systematic review. Diabet Med. 2000 Oct;17(10):693-9. [Article]
  5. Bressolle F, Costa P, Rouzier-Panis R, Marquer C: Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5. [Article]
  6. Costa P, Bressolle F, Jarroux E, Sarrazin B, Mosser J, Navratil H, Galtier M: Multiple-dose pharmacokinetics of moxisylyte after oral administration to healthy volunteers. J Pharm Sci. 1993 Sep;82(9):968-71. [Article]
  7. Costa P, Bressolle F, Bromet-Petit M, Mosser J, Sarrazin B: Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and oral administration. J Pharm Sci. 1992 Dec;81(12):1223-6. [Article]
  8. Costa P, Bressolle F, Sarrazin B, Mosser J, Galtier M: Pharmacokinetics of moxisylyte in healthy volunteers after intravenous and intracavernous administration. J Pharm Sci. 1993 Jul;82(7):729-33. [Article]
  9. WHO (1987). WHO drug information (4th ed.). WHO.
  10. Ellis G.P. and West G.B. (1986). Progress in Medicinal Chemistry Volume 23. Elsevier.
  11. FDA-orphan products [Link]
  12. Eye wiki [Link]
  13. Opilon monograph [Link]
  14. Jstage [Link]
Human Metabolome Database
HMDB0254909
KEGG Drug
D08239
PubChem Compound
4260
PubChem Substance
310265113
ChemSpider
4110
BindingDB
50452139
RxNav
10561
ChEBI
94754
ChEMBL
CHEMBL159226
ZINC
ZINC000000057401
Wikipedia
Moxisylyte
MSDS
Download (42 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Pill
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145ºCUnited States Environmental Protection Agency.
boiling point (°C)371ºC at 760 mmHg'MSDS'
water solubility>47.4 ug/mlBurnham Center for Chemical Genomics
logP3.17United States Environmental Protection Agency.
pKa8.71Microphysiology Database Project. University of Pittsburgh.
Predicted Properties
PropertyValueSource
Water Solubility0.406 mg/mLALOGPS
logP3.22ALOGPS
logP3.2Chemaxon
logS-2.8ALOGPS
pKa (Strongest Basic)8.79Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area38.77 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity80.9 m3·mol-1Chemaxon
Polarizability32.39 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9220000000-68bd4629f9c0568eb1d3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05fr-6590000000-bbbd3a6a2728f1ecf30c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-2900000000-fc80ad94949eaff79550
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9300000000-02430ea9f61efb605fff
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9100000000-b06e6e0141257eb4f266
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9500000000-b29f749aaf23bc108fc8
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-9100000000-d8b0e28f2de904ef7b8a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-177.9529645
predicted
DarkChem Lite v0.1.0
[M-H]-173.62834
predicted
DeepCCS 1.0 (2019)
[M+H]+179.3306645
predicted
DarkChem Lite v0.1.0
[M+H]+175.98634
predicted
DeepCCS 1.0 (2019)
[M+Na]+178.3891645
predicted
DarkChem Lite v0.1.0
[M+Na]+182.07948
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Alpha adrenergic receptor (Protein Group)
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
NameUniProt ID
Alpha-1A adrenergic receptorP35348
Alpha-1B adrenergic receptorP35368
Alpha-1D adrenergic receptorP25100
Alpha-2A adrenergic receptorP08913
Alpha-2B adrenergic receptorP18089
Alpha-2C adrenergic receptorP18825
References
  1. Wand M, Grant WM: Thymoxamine hydrochloride: an alpha-adrenergic blocker. Surv Ophthalmol. 1980 Sep-Oct;25(2):75-84. [Article]

Enzymes

Details1. Cholinesterase
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Bressolle F, Costa P, Rouzier-Panis R, Marquer C: Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5. [Article]
  2. Jstage [Link]
Details2. Cytochrome P450 3A Subfamily (Protein Group)
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Components:
NameUniProt ID
Cytochrome P450 3A4P08684
Cytochrome P450 3A43Q9HB55
Cytochrome P450 3A5P20815
Cytochrome P450 3A7P24462
References
  1. Jstage [Link]

Drug created at October 19, 2015 20:13 / Updated at October 13, 2023 20:31