Identification

Name
Dapiprazole
Accession Number
DB00298  (APRD00902)
Type
Small Molecule
Groups
Approved
Description

Dapiprazole (U.S. trade name Rev-Eyes) is an alpha blocker. It is used to reverse mydriasis after eye examination. [Wikipedia]

Structure
Thumb
Synonyms
  • 5,6,7,8-Tetrahydro-3-(2-(4-(O-tolyl)-1-piperazinyl)ethyl)-S-triazolo(4,3-a)pyridine
  • Dapiprazol
  • Dapiprazolum
Product Ingredients
IngredientUNIICASInChI Key
Dapiprazole hydrochlorideDS9UJN1I0X72822-13-0ZIODNPFQZIHCOE-UHFFFAOYSA-N
International/Other Brands
Rev-Eyes
Categories
UNII
5RNZ8GJO7K
CAS number
72822-12-9
Weight
Average: 325.4512
Monoisotopic: 325.226645889
Chemical Formula
C19H27N5
InChI Key
RFWZESUMWJKKRN-UHFFFAOYSA-N
InChI
InChI=1S/C19H27N5/c1-16-6-2-3-7-17(16)23-14-12-22(13-15-23)11-9-19-21-20-18-8-4-5-10-24(18)19/h2-3,6-7H,4-5,8-15H2,1H3
IUPAC Name
1-(2-methylphenyl)-4-(2-{5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyridin-3-yl}ethyl)piperazine
SMILES
CC1=CC=CC=C1N1CCN(CCC2=NN=C3CCCCN23)CC1

Pharmacology

Indication

Used in the treatment of iatrogenically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents used in certain eye examinations.

Pharmacodynamics

Dapiprazole is an alpha-adrenergic blocking agent. It produces miosis by blocking the alpha-adrenergic receptors on the dilator muscle of the iris. Dapiprazole produces no significant action on ciliary muscle contraction and thus, there are no changes in the depth of the anterior chamber of the thickness of the lens. It does not alter the IOP either in normal eyes or in eyes with elevated IOP. The rate of pupillary constriction may be slightly slower in clients with brown irises than in clients with blue or green irises.

Mechanism of action

Dapiprazole acts through blocking the alpha1-adrenergic receptors in smooth muscle. It produces miosis through an effect on the dilator muscle of the iris and does not have any significant activity on ciliary muscle contraction and, therefore does not induce a significant change in the anterior chamber depth or the thickness of the lens.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Human
AAlpha-1D adrenergic receptor
antagonist
Human
AAlpha-1B adrenergic receptor
antagonist
Human
Absorption

Systemic absorption is negligible.

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

Oral LD50 is 1189-2100 mg/kg in mice, rats and rabbits.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineDapiprazole may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineDapiprazole may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineDapiprazole may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineDapiprazole may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineDapiprazole may decrease the vasoconstricting activities of 4-Methoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with 7-Nitroindazole.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Dapiprazole.
AcepromazineDapiprazole may increase the antihypertensive activities of Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Aceprometazine.
AdipiplonThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Adipiplon.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014443
PubChem Compound
3033538
PubChem Substance
46508859
ChemSpider
2298190
ChEBI
51066
ChEMBL
CHEMBL1201216
Therapeutic Targets Database
DAP000298
PharmGKB
PA164749109
Drugs.com
Drugs.com Drug Page
Wikipedia
Dapiprazole
ATC Codes
S01EX02 — Dapiprazole
MSDS
Download (114 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Angelini pharmaceuticals inc
Packagers
  • American Cyanamid Co.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.751 mg/mLALOGPS
logP2.78ALOGPS
logP2.42ChemAxon
logS-2.6ALOGPS
pKa (Strongest Basic)7.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area37.19 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity100.22 m3·mol-1ChemAxon
Polarizability38.23 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9832
Caco-2 permeable+0.5899
P-glycoprotein substrateSubstrate0.657
P-glycoprotein inhibitor IInhibitor0.8074
P-glycoprotein inhibitor IIInhibitor0.9107
Renal organic cation transporterInhibitor0.7481
CYP450 2C9 substrateNon-substrate0.8296
CYP450 2D6 substrateNon-substrate0.5563
CYP450 3A4 substrateSubstrate0.5833
CYP450 1A2 substrateInhibitor0.6905
CYP450 2C9 inhibitorNon-inhibitor0.5324
CYP450 2D6 inhibitorNon-inhibitor0.632
CYP450 2C19 inhibitorInhibitor0.7506
CYP450 3A4 inhibitorInhibitor0.7338
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9357
Ames testNon AMES toxic0.6215
CarcinogenicityNon-carcinogens0.8546
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7573 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6592
hERG inhibition (predictor II)Inhibitor0.7292
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 phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Triazolopyridines / Dialkylarylamines / Aniline and substituted anilines / Aminotoluenes / N-alkylpiperazines / Aralkylamines / Pyridines and derivatives / Triazoles / Heteroaromatic compounds
show 4 more
Substituents
Phenylpiperazine / N-arylpiperazine / Triazolopyridine / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines / Aminotoluene / Aralkylamine / N-alkylpiperazine / Toluene
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, pyridines, N-alkylpiperazine (CHEBI:51066)

Targets

Kind
Protein
Organism
Human
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...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Eltze M: Affinity of the miotic drug, dapiprazole, at alpha 1-adrenoceptor subtypes A, B and D. J Pharm Pharmacol. 1997 Nov;49(11):1091-5. [PubMed:9401944]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
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...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:54