This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Dotarizine
Accession Number
DB06446
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • dotarizina
Categories
UNII
IO7663S6D3
CAS number
84625-59-2
Weight
Average: 442.5925
Monoisotopic: 442.262028342
Chemical Formula
C29H34N2O2
InChI Key
LRMJAFKKJLRDLE-UHFFFAOYSA-N
InChI
InChI=1S/C29H34N2O2/c1-4-11-25(12-5-1)28(26-13-6-2-7-14-26)31-21-19-30(20-22-31)18-10-17-29(32-23-24-33-29)27-15-8-3-9-16-27/h1-9,11-16,28H,10,17-24H2
IUPAC Name
1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl)propyl]piperazine
SMILES
C(CN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1)CC1(OCCO1)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in migraine and cluster headaches.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
U5-hydroxytryptamine receptor 2ANot AvailableHuman
U5-hydroxytryptamine receptor 1ANot AvailableHuman
UVoltage-dependent P/Q-type calcium channel subunit alpha-1ANot AvailableHuman
U5-hydroxytryptamine receptor 2CNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Dotarizine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Dotarizine is combined with (S)-Warfarin.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Dotarizine is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Dotarizine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Dotarizine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Dotarizine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Dotarizine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Dotarizine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Dotarizine.
5-androstenedioneThe metabolism of Dotarizine can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
55285
ChemSpider
49929
ChEBI
138033
ChEMBL
CHEMBL2106316
Wikipedia
Dotarizine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00339 mg/mLALOGPS
logP4.62ALOGPS
logP5.91ChemAxon
logS-5.1ALOGPS
pKa (Strongest Basic)8.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area24.94 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity134.13 m3·mol-1ChemAxon
Polarizability51.47 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9661
Blood Brain Barrier+0.9869
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.5606
P-glycoprotein inhibitor INon-inhibitor0.5661
P-glycoprotein inhibitor IINon-inhibitor0.7562
Renal organic cation transporterInhibitor0.6695
CYP450 2C9 substrateNon-substrate0.8982
CYP450 2D6 substrateNon-substrate0.6457
CYP450 3A4 substrateNon-substrate0.6014
CYP450 1A2 substrateNon-inhibitor0.6406
CYP450 2C9 inhibitorNon-inhibitor0.7607
CYP450 2D6 inhibitorNon-inhibitor0.5786
CYP450 2C19 inhibitorNon-inhibitor0.7097
CYP450 3A4 inhibitorNon-inhibitor0.8237
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6342
Ames testNon AMES toxic0.7679
CarcinogenicityNon-carcinogens0.926
BiodegradationNot ready biodegradable0.9929
Rat acute toxicity3.0172 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8214
hERG inhibition (predictor II)Non-inhibitor0.5385
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 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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenylbutylamines / N-alkylpiperazines / Ketals / Aralkylamines / 1,3-dioxolanes / Trialkylamines / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Phenylbutylamine / Ketal / N-alkylpiperazine / Aralkylamine / 1,4-diazinane / Piperazine / Meta-dioxolane / Tertiary amine / Tertiary aliphatic amine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Belcheva S, Petkov VD, Konstantinova E, Petkov VV, Boyanova E: Effects on nociception of the Ca2+ and 5-HT antagonist dotarizine and other 5-HT receptor agonists and antagonists. Acta Physiol Pharmacol Bulg. 1995;21(4):93-8. [PubMed:8830881]
  2. Farre M, Roset PN, Llorente M, Marquez M, Albet C, Perez JA, Herrero E, Ortiz JA: Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration. Methods Find Exp Clin Pharmacol. 1997 Jun;19(5):343-50. [PubMed:9379783]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Belcheva S, Petkov VD, Konstantinova E, Petkov VV, Boyanova E: Effects on nociception of the Ca2+ and 5-HT antagonist dotarizine and other 5-HT receptor agonists and antagonists. Acta Physiol Pharmacol Bulg. 1995;21(4):93-8. [PubMed:8830881]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1A
Uniprot ID
O00555
Uniprot Name
Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Molecular Weight
282362.39 Da
References
  1. Ruiz-Nuno A, Mayorgas I, Hernandez-Guijo JM, Olivares R, Garcia AG, Gandia L: Antimigraine dotarizine blocks P/Q Ca2+ channels and exocytosis in a voltage-dependent manner in chromaffin cells. Eur J Pharmacol. 2003 Nov 14;481(1):41-50. [PubMed:14637173]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Farre M, Roset PN, Llorente M, Marquez M, Albet C, Perez JA, Herrero E, Ortiz JA: Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration. Methods Find Exp Clin Pharmacol. 1997 Jun;19(5):343-50. [PubMed:9379783]

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 March 19, 2008 10:33 / Updated on November 02, 2018 06:16