Dotarizine
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This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Summary
Dotarizine is a calcium antagonist used to treat and prevent migraines.
- Generic Name
- Dotarizine
- DrugBank Accession Number
- DB06446
- Background
Not Available
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 442.5925
Monoisotopic: 442.262028342 - Chemical Formula
- C29H34N2O2
- Synonyms
- dotarizina
- Dotarizine
Pharmacology
- Indication
Investigated for use/treatment in migraine and cluster headaches.
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- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism U5-hydroxytryptamine receptor 2A Not Available Humans U5-hydroxytryptamine receptor 1A Not Available Humans UVoltage-dependent P/Q-type calcium channel subunit alpha-1A Not Available Humans U5-hydroxytryptamine receptor 2C Not Available Humans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Dotarizine is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Dotarizine can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Dotarizine is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Dotarizine. Aceclofenac The risk or severity of hyperkalemia can be increased when Dotarizine is combined with Aceclofenac. - Food Interactions
- Not Available
Categories
- Drug Categories
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antidepressive Agents
- Benzene Derivatives
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Membrane Transport Modulators
- Neurotransmitter Agents
- Serotonin Agents
- Serotonin Receptor Antagonists
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,4-diazinane / Acetal / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Diphenylmethane / Hydrocarbon derivative / Ketal / Meta-dioxolane
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- IO7663S6D3
- CAS number
- 84625-59-2
- 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
References
- General References
- Not Available
- External Links
- PubChem Compound
- 55285
- ChemSpider
- 49929
- ChEBI
- 138033
- ChEMBL
- CHEMBL2106316
- ZINC
- ZINC000022058279
- Wikipedia
- Dotarizine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
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
Property Value Source Water Solubility 0.00339 mg/mL ALOGPS logP 4.62 ALOGPS logP 5.91 Chemaxon logS -5.1 ALOGPS pKa (Strongest Basic) 8.28 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 24.94 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 134.13 m3·mol-1 Chemaxon Polarizability 51.47 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9661 Blood Brain Barrier + 0.9869 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.5606 P-glycoprotein inhibitor I Non-inhibitor 0.5661 P-glycoprotein inhibitor II Non-inhibitor 0.7562 Renal organic cation transporter Inhibitor 0.6695 CYP450 2C9 substrate Non-substrate 0.8982 CYP450 2D6 substrate Non-substrate 0.6457 CYP450 3A4 substrate Non-substrate 0.6014 CYP450 1A2 substrate Non-inhibitor 0.6406 CYP450 2C9 inhibitor Non-inhibitor 0.7607 CYP450 2D6 inhibitor Non-inhibitor 0.5786 CYP450 2C19 inhibitor Non-inhibitor 0.7097 CYP450 3A4 inhibitor Non-inhibitor 0.8237 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6342 Ames test Non AMES toxic 0.7679 Carcinogenicity Non-carcinogens 0.926 Biodegradation Not ready biodegradable 0.9929 Rat acute toxicity 3.0172 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8214 hERG inhibition (predictor II) Non-inhibitor 0.5385
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0007-0005900000-d4f8e11115ec5c430375 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0007-0004900000-2382ef06ef3c79feb88f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-02tc-1203900000-1983a47e46bc953f7f2d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-8008900000-e655b02cadee90b78463 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-014l-7904300000-d1b69250bc0dfb9692a7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0ik9-0981300000-2195cb235388338ceef6 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 223.5241201 predictedDarkChem Lite v0.1.0 [M-H]- 200.71107 predictedDeepCCS 1.0 (2019) [M+H]+ 223.8420201 predictedDarkChem Lite v0.1.0 [M+H]+ 203.10664 predictedDeepCCS 1.0 (2019) [M+Na]+ 223.0071201 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.28172 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
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1. Details5-hydroxytryptamine receptor 2A
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- 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. [Article]
2. Details5-hydroxytryptamine receptor 1A
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
4. Details5-hydroxytryptamine receptor 2C
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
Enzymes
1. DetailsCytochrome P450 3A4
- Kind
- Protein
- 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...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
Drug created at March 19, 2008 16:33 / Updated at June 19, 2021 00:26