Dotarizine

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
Not Available
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.

Structured Indications
Not Available
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
DrugInteractionDrug group
2-HYDROXY-1,4-NAPHTHOQUINONEThe therapeutic efficacy of 2-HYDROXY-1,4-NAPHTHOQUINONE can be increased when used in combination with Dotarizine.Experimental
2-mercaptobenzothiazoleThe therapeutic efficacy of 2-mercaptobenzothiazole can be increased when used in combination with Dotarizine.Vet Approved
AlfuzosinThe risk or severity of hypotension can be increased when Alfuzosin is combined with Dotarizine.Approved, Investigational
AmobarbitalThe metabolism of Dotarizine can be increased when combined with Amobarbital.Approved, Illicit
AmorolfineThe therapeutic efficacy of Amorolfine can be increased when used in combination with Dotarizine.Approved, Investigational
Amphotericin BThe therapeutic efficacy of Amphotericin B can be increased when used in combination with Dotarizine.Approved, Investigational
AnidulafunginThe therapeutic efficacy of Anidulafungin can be increased when used in combination with Dotarizine.Approved, Investigational
ArotinololThe risk or severity of hypotension, conduction block, and bradycardia can be increased when Arotinolol is combined with Dotarizine.Investigational
ArtemetherThe therapeutic efficacy of Artemether can be increased when used in combination with Dotarizine.Approved
Bafilomycin A1The therapeutic efficacy of Bafilomycin A1 can be increased when used in combination with Dotarizine.Experimental
BarbexacloneThe metabolism of Dotarizine can be increased when combined with Barbexaclone.Experimental
BarbitalThe metabolism of Dotarizine can be increased when combined with Barbital.Illicit
Benzoic AcidThe therapeutic efficacy of Benzoic Acid can be increased when used in combination with Dotarizine.Approved, Investigational
BifonazoleThe therapeutic efficacy of Bifonazole can be increased when used in combination with Dotarizine.Approved, Investigational
Brefeldin AThe therapeutic efficacy of Brefeldin A can be increased when used in combination with Dotarizine.Experimental
BucindololThe risk or severity of hypotension can be increased when Bucindolol is combined with Dotarizine.Investigational
BunazosinThe risk or severity of hypotension can be increased when Bunazosin is combined with Dotarizine.Investigational
ButenafineThe therapeutic efficacy of Butenafine can be increased when used in combination with Dotarizine.Approved
ButoconazoleThe therapeutic efficacy of Butoconazole can be increased when used in combination with Dotarizine.Approved
Calcium AcetateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium Acetate.Approved, Investigational
Calcium ChlorideThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium Chloride.Approved
Calcium CitrateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium Citrate.Approved
Calcium glubionateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium glubionate.Approved
Calcium GluceptateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium Gluceptate.Approved
Calcium gluconateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium lactate gluconate.Experimental
Calcium levulinateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium levulinate.Approved, Experimental
Calcium pangamateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium pangamate.Experimental
Calcium PhosphateThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Calcium Phosphate.Approved
CandicidinThe therapeutic efficacy of Candicidin can be increased when used in combination with Dotarizine.Withdrawn
Capric acidThe therapeutic efficacy of Capric acid can be increased when used in combination with Dotarizine.Experimental
CarvedilolThe risk or severity of hypotension can be increased when Carvedilol is combined with Dotarizine.Approved, Investigational
CaseinThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Casein.Approved
CaspofunginThe therapeutic efficacy of Caspofungin can be increased when used in combination with Dotarizine.Approved
CeruleninThe therapeutic efficacy of Cerulenin can be increased when used in combination with Dotarizine.Approved
ChloroxineThe therapeutic efficacy of Chloroxine can be increased when used in combination with Dotarizine.Approved
CiclopiroxThe therapeutic efficacy of Ciclopirox can be increased when used in combination with Dotarizine.Approved, Investigational
CimetidineThe serum concentration of Dotarizine can be increased when it is combined with Cimetidine.Approved, Investigational
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Dotarizine.Approved
ClotrimazoleThe therapeutic efficacy of Clotrimazole can be increased when used in combination with Dotarizine.Approved, Vet Approved
CordycepinThe therapeutic efficacy of Cordycepin can be increased when used in combination with Dotarizine.Investigational
CyclosporineThe therapeutic efficacy of Cyclosporine can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
DichloropheneThe therapeutic efficacy of Dichlorophene can be increased when used in combination with Dotarizine.Vet Approved
DoxazosinThe risk or severity of hypotension can be increased when Doxazosin is combined with Dotarizine.Approved
EconazoleThe therapeutic efficacy of Econazole can be increased when used in combination with Dotarizine.Approved
EfavirenzThe serum concentration of Dotarizine can be decreased when it is combined with Efavirenz.Approved, Investigational
EfinaconazoleThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Dotarizine.Approved
FenticonazoleThe therapeutic efficacy of Fenticonazole can be increased when used in combination with Dotarizine.Experimental
FluconazoleThe therapeutic efficacy of Fluconazole can be increased when used in combination with Dotarizine.Approved, Investigational
FlucytosineThe therapeutic efficacy of Flucytosine can be increased when used in combination with Dotarizine.Approved, Investigational
FlutrimazoleThe therapeutic efficacy of Flutrimazole can be increased when used in combination with Dotarizine.Experimental
GlyphosateThe therapeutic efficacy of Glyphosate can be increased when used in combination with Dotarizine.Experimental
GriseofulvinThe therapeutic efficacy of Griseofulvin can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
HachimycinThe therapeutic efficacy of Hachimycin can be increased when used in combination with Dotarizine.Experimental
HaloproginThe therapeutic efficacy of Haloprogin can be increased when used in combination with Dotarizine.Approved, Withdrawn
HexetidineThe therapeutic efficacy of Hexetidine can be increased when used in combination with Dotarizine.Approved, Investigational
HexobarbitalThe metabolism of Dotarizine can be increased when combined with Hexobarbital.Approved
IndoraminThe risk or severity of hypotension can be increased when Indoramin is combined with Dotarizine.Withdrawn
IsoconazoleThe therapeutic efficacy of Isoconazole can be increased when used in combination with Dotarizine.Approved
ItraconazoleThe therapeutic efficacy of Itraconazole can be increased when used in combination with Dotarizine.Approved, Investigational
KetoconazoleThe therapeutic efficacy of Ketoconazole can be increased when used in combination with Dotarizine.Approved, Investigational
LabetalolThe risk or severity of hypotension can be increased when Labetalol is combined with Dotarizine.Approved
Magnesium hydroxideThe risk or severity of hypotension and neuromuscular blockade can be increased when Dotarizine is combined with Magnesium hydroxide.Approved, Investigational
Magnesium oxideThe risk or severity of hypotension and neuromuscular blockade can be increased when Dotarizine is combined with Magnesium oxide.Approved
Magnesium salicylateThe risk or severity of hypotension and neuromuscular blockade can be increased when Dotarizine is combined with Magnesium salicylate.Approved
Magnesium sulfateThe risk or severity of hypotension and neuromuscular blockade can be increased when Dotarizine is combined with Magnesium sulfate.Approved, Investigational, Vet Approved
MepartricinThe therapeutic efficacy of Mepartricin can be increased when used in combination with Dotarizine.Experimental
MethohexitalThe metabolism of Dotarizine can be increased when combined with Methohexital.Approved
MethylphenobarbitalThe metabolism of Dotarizine can be increased when combined with Methylphenobarbital.Approved
MevastatinThe therapeutic efficacy of Mevastatin can be increased when used in combination with Dotarizine.Experimental
MicafunginThe therapeutic efficacy of Micafungin can be increased when used in combination with Dotarizine.Approved, Investigational
MiconazoleThe therapeutic efficacy of Miconazole can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
MiltefosineThe therapeutic efficacy of Miltefosine can be increased when used in combination with Dotarizine.Approved, Investigational
MonensinThe therapeutic efficacy of Monensin can be increased when used in combination with Dotarizine.Vet Approved
MyxothiazolThe therapeutic efficacy of Myxothiazol can be increased when used in combination with Dotarizine.Experimental
NafcillinThe therapeutic efficacy of Dotarizine can be decreased when used in combination with Nafcillin.Approved, Investigational
NaftifineThe therapeutic efficacy of Naftifine can be increased when used in combination with Dotarizine.Approved
NatamycinThe therapeutic efficacy of Natamycin can be increased when used in combination with Dotarizine.Approved
NifuratelThe therapeutic efficacy of Nifuratel can be increased when used in combination with Dotarizine.Experimental
Nikkomycin ZThe therapeutic efficacy of Nikkomycin Z can be increased when used in combination with Dotarizine.Investigational
NitroprussideDotarizine may increase the hypotensive activities of Nitroprusside.Approved, Investigational
NitroxolineThe therapeutic efficacy of Nitroxoline can be increased when used in combination with Dotarizine.Approved
NystatinThe therapeutic efficacy of Nystatin can be increased when used in combination with Dotarizine.Approved, Vet Approved
OmoconazoleThe therapeutic efficacy of Omoconazole can be increased when used in combination with Dotarizine.Experimental
OxiconazoleThe therapeutic efficacy of Oxiconazole can be increased when used in combination with Dotarizine.Approved
PafuramidineThe therapeutic efficacy of Pafuramidine can be increased when used in combination with Dotarizine.Investigational
PentamidineThe therapeutic efficacy of Pentamidine can be increased when used in combination with Dotarizine.Approved, Investigational
PentobarbitalThe metabolism of Dotarizine can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Dotarizine can be increased when combined with Phenobarbital.Approved, Investigational
PosaconazoleThe therapeutic efficacy of Posaconazole can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
PrazosinThe risk or severity of hypotension can be increased when Prazosin is combined with Dotarizine.Approved
PrimidoneThe metabolism of Dotarizine can be increased when combined with Primidone.Approved, Vet Approved
PyrrolnitrinThe therapeutic efficacy of Pyrrolnitrin can be increased when used in combination with Dotarizine.Experimental
RadicicolThe therapeutic efficacy of Radicicol can be increased when used in combination with Dotarizine.Experimental
RifabutinThe risk or severity of hypotension can be increased when Rifabutin is combined with Dotarizine.Approved, Investigational
RifampicinThe risk or severity of hypotension can be increased when Rifampicin is combined with Dotarizine.Approved
RifapentineThe risk or severity of hypotension can be increased when Rifapentine is combined with Dotarizine.Approved, Investigational
RifaximinThe risk or severity of hypotension can be increased when Rifaximin is combined with Dotarizine.Approved, Investigational
Salicylhydroxamic AcidThe therapeutic efficacy of Salicylhydroxamic Acid can be increased when used in combination with Dotarizine.Experimental
Salicylic acidThe therapeutic efficacy of Salicylic acid can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
SecobarbitalThe metabolism of Dotarizine can be increased when combined with Secobarbital.Approved, Vet Approved
SertaconazoleThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Dotarizine.Approved, Investigational
SilodosinThe risk or severity of hypotension can be increased when Silodosin is combined with Dotarizine.Approved
SinefunginThe therapeutic efficacy of Sinefungin can be increased when used in combination with Dotarizine.Experimental
SirolimusThe therapeutic efficacy of Sirolimus can be increased when used in combination with Dotarizine.Approved, Investigational
SulconazoleThe therapeutic efficacy of Sulconazole can be increased when used in combination with Dotarizine.Approved
TamsulosinThe risk or severity of hypotension can be increased when Tamsulosin is combined with Dotarizine.Approved, Investigational
TavaboroleThe therapeutic efficacy of Tavaborole can be increased when used in combination with Dotarizine.Approved, Investigational
TerazosinThe risk or severity of hypotension can be increased when Terazosin is combined with Dotarizine.Approved
TerbinafineThe therapeutic efficacy of Terbinafine can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
TerconazoleThe therapeutic efficacy of Terconazole can be increased when used in combination with Dotarizine.Approved
ThiamylalThe metabolism of Dotarizine can be increased when combined with Thiamylal.Approved, Vet Approved
ThiopentalThe metabolism of Dotarizine can be increased when combined with Thiopental.Approved, Vet Approved
ThymolThe therapeutic efficacy of Thymol can be increased when used in combination with Dotarizine.Approved
TioconazoleThe therapeutic efficacy of Tioconazole can be increased when used in combination with Dotarizine.Approved
TolciclateThe therapeutic efficacy of Tolciclate can be increased when used in combination with Dotarizine.Experimental
TolnaftateThe therapeutic efficacy of Tolnaftate can be increased when used in combination with Dotarizine.Approved, Investigational, Vet Approved
TrimazosinThe risk or severity of hypotension can be increased when Trimazosin is combined with Dotarizine.Experimental
TrimetrexateThe therapeutic efficacy of Trimetrexate can be increased when used in combination with Dotarizine.Approved, Investigational
UrapidilThe risk or severity of hypotension can be increased when Urapidil is combined with Dotarizine.Investigational
VoriconazoleThe therapeutic efficacy of Voriconazole can be increased when used in combination with Dotarizine.Approved, Investigational
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]

Drug created on March 19, 2008 10:33 / Updated on March 02, 2018 03:09