Identification

Name
Cyclandelate
Accession Number
DB04838
Type
Small Molecule
Groups
Approved
Description

A direct-acting smooth muscle relaxant used to dilate blood vessels. It may cause gastrointestinal distress and tachycardia. Cyclandelate is not approved for use in the U.S. or Canada, but is approved in various European countries.

Structure
Thumb
Synonyms
  • 3,3,5-Trimethylcyclohexyl mandelate
  • 3,5,5-Trimethylcyclohexyl amygdalate
  • Ciclandelato
  • Cyclandelatum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cyclospasmol Tablets 200mgTablet200 mgOralWyeth Ayerst Canada Inc.1994-12-311997-08-14Canada
International/Other Brands
Capilan (Takeda) / Cyclergine / Cyclospasmol (lves)
Categories
UNII
4139O1OAY2
CAS number
456-59-7
Weight
Average: 276.3707
Monoisotopic: 276.172544634
Chemical Formula
C17H24O3
InChI Key
WZHCOOQXZCIUNC-UHFFFAOYSA-N
InChI
InChI=1S/C17H24O3/c1-12-9-14(11-17(2,3)10-12)20-16(19)15(18)13-7-5-4-6-8-13/h4-8,12,14-15,18H,9-11H2,1-3H3
IUPAC Name
3,3,5-trimethylcyclohexyl 2-hydroxy-2-phenylacetate
SMILES
CC1CC(CC(C)(C)C1)OC(=O)C(O)C1=CC=CC=C1

Pharmacology

Indication

Used in the treatment of various blood vessel diseases (e.g., claudication, arteriosclerosis and Raynaud's disease) and nighttime leg cramps.

Pharmacodynamics

Cyclandelate is in a class of drugs called vasodilators. Cyclandelate relaxes veins and arteries, which makes them wider and allows blood to pass through them more easily.

Mechanism of action

Cyclandelate produces peripheral vasodilation by a direct effect on vascular smooth muscle. Pharmacological action may be due to calcium-channel antagonism.

TargetActionsOrganism
UVoltage-dependent calcium channel subunit alpha-2/delta-1
inhibitor
Human
ULiver carboxylesterase 1Not AvailableHuman
Absorption

Well absorbed following oral administration.

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

Acute oral toxicity (LD50): 3950 mg/kg [Guinea pig]

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

Interactions

Drug Interactions
DrugInteraction
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Cyclandelate.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Cyclandelate.
AlbaconazoleThe therapeutic efficacy of Albaconazole can be increased when used in combination with Cyclandelate.
AlclometasoneThe metabolism of Cyclandelate can be decreased when combined with Alclometasone.
AlcuroniumCyclandelate may increase the neuromuscular blocking activities of Alcuronium.
AlfuzosinThe risk or severity of hypotension can be increased when Alfuzosin is combined with Cyclandelate.
AmcinonideThe metabolism of Cyclandelate can be decreased when combined with Amcinonide.
Aminosalicylic AcidCyclandelate may increase the anticoagulant activities of Aminosalicylic Acid.
AmiodaroneThe metabolism of Cyclandelate can be decreased when combined with Amiodarone.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Cyclandelate.
Food Interactions
  • Take with food to reduce irritation.

References

Synthesis Reference

Nauta, W.T.; U.S. Patent 2,707,193; April 26,1955; assigned to N.V. Koninklijke Pharmaceutische Fabrieken Voorbeen Brocades Stheeman & Pharmacia, Netherlands. Flitter, D.; U.S. Patent 3,663,597; May 16, 1972; assigned to American Home Products Corporation.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015586
PubChem Compound
2893
PubChem Substance
46505740
ChemSpider
2790
ChEBI
3988
ChEMBL
CHEMBL1480987
PharmGKB
PA164748026
Drugs.com
Drugs.com Drug Page
Wikipedia
Cyclandelate
ATC Codes
C04AX01 — Cyclandelate
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Spectrum Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral200 mg
Prices
Unit descriptionCostUnit
Cyclandelate powder8.18USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)50-53Nauta, W.T.; U.S. Patent 2,707,193; April 26,1955; assigned to N.V. Koninklijke Pharmaceutische Fabrieken Voorbeen Brocades Stheeman & Pharmacia, Netherlands.
boiling point (°C)193 °C at 1.40E+01 mm HgPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0997 mg/mLALOGPS
logP3.79ALOGPS
logP3.72ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)11.99ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity78.06 m3·mol-1ChemAxon
Polarizability30.95 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.8761
Caco-2 permeable+0.7443
P-glycoprotein substrateNon-substrate0.551
P-glycoprotein inhibitor IInhibitor0.6324
P-glycoprotein inhibitor IINon-inhibitor0.6209
Renal organic cation transporterNon-inhibitor0.8746
CYP450 2C9 substrateNon-substrate0.7769
CYP450 2D6 substrateNon-substrate0.9047
CYP450 3A4 substrateSubstrate0.6148
CYP450 1A2 substrateNon-inhibitor0.8485
CYP450 2C9 inhibitorInhibitor0.7116
CYP450 2D6 inhibitorNon-inhibitor0.9365
CYP450 2C19 inhibitorNon-inhibitor0.7518
CYP450 3A4 inhibitorNon-inhibitor0.9024
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9469
Ames testNon AMES toxic0.8703
CarcinogenicityNon-carcinogens0.7047
BiodegradationNot ready biodegradable0.9626
Rat acute toxicity1.7115 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Non-inhibitor0.8132
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Secondary alcohols / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Aromatic alcohols
Substituents
Monocyclic benzene moiety / Secondary alcohol / Carboxylic acid ester / Monocarboxylic acid or derivatives / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Aromatic alcohol / Organooxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carboxylic ester, secondary alcohol (CHEBI:3988)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
Gene Name
CACNA2D1
Uniprot ID
P54289
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight
124566.93 Da
References
  1. Pascual J: [New prospects in the treatment of migraine]. Neurologia. 1999 Dec;14 Suppl 6:26-35. [PubMed:10659603]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Heffron F, Middleton B, White DA: Inhibition of acyl coenzyme A: cholesterol acyl transferase by trimethylcyclohexanylmandelate (cyclandelate). Biochem Pharmacol. 1990 Feb 1;39(3):575-80. [PubMed:2306268]

Enzymes

Kind
Protein
Organism
Human
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...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [PubMed:22039822]

Drug created on September 26, 2007 09:09 / Updated on August 26, 2018 02:00