Identification

Name
Pirenzepine
Accession Number
DB00670  (APRD00515)
Type
Small Molecule
Groups
Approved
Description

An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as cimetidine and ranitidine. It is generally well tolerated by patients. [PubChem]

Structure
Thumb
Synonyms
  • 11-((4-Methyl-1-piperazinyl)acetyl)-5,11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-one
  • Pirenzepin
  • Pirenzepina
  • Pirenzépine
  • Pirenzepinum
External IDs
ACI-91 / L-S519
Product Ingredients
IngredientUNIICASInChI Key
Pirenzepine Hydrochloride10YM403FLS29868-97-1FFNMBRCFFADNAO-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gastrozepin Tab 50mgTablet50 mgOralBoehringer Ingelheim (Canada) Ltd Ltee1984-12-311996-09-09Canada
International/Other Brands
Anquwei (Panion & BF) / Folinzepin (Tsuruhara Seiyaku) / Garendopine (Choseido Pharmaceutical) / Gaspin (Gentle) / Gastrozepin (Boehringer Ingelheim) / Gastsion (Shiono Kemikaru) / Gaszepin (Swiss Pharm) / Karoderin (Nippon Chemiphar) / Kawaipin (Siu Guan) / Kiccalzin (Takata Seiyaku) / Lizepine (Health Chemical) / Lonzepin (Li Ta) / Muszepin (Royal) / Pilenzel (Taiyo Pharmaceutical) / Pin (Tatsumi Kagaku) / Pirepine (Yu Sheng) / Pirodeine (Medisa Shinyaku) / Pizepine (Yuan Chou) / Ranclic (Towa Yakuhin) / Regastric (Jinup) / Stomazepin (Taisho Yakuhin) / Ulopine (Panbiotic)
Categories
UNII
3G0285N20N
CAS number
28797-61-7
Weight
Average: 351.4023
Monoisotopic: 351.169524941
Chemical Formula
C19H21N5O2
InChI Key
RMHMFHUVIITRHF-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N5O2/c1-22-9-11-23(12-10-22)13-17(25)24-16-7-3-2-5-14(16)19(26)21-15-6-4-8-20-18(15)24/h2-8H,9-13H2,1H3,(H,21,26)
IUPAC Name
2-[2-(4-methylpiperazin-1-yl)acetyl]-2,4,9-triazatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3(8),4,6,11,13-hexaen-10-one
SMILES
CN1CCN(CC(=O)N2C3=CC=CC=C3C(=O)NC3=C2N=CC=C3)CC1

Pharmacology

Indication

For the treatment of peptic ulcer, gastric ulcer, and duodenal ulcer.

Pharmacodynamics

Pirenzepine belongs to a group of medications called antispasmodics/anticholinergics. These medications are used to relieve cramps or spasms of the stomach, intestines, and bladder. Pirenzepine is used to treat duodenal or stomach ulcers or intestine problems. It can be used together with antacids or other medicine in the treatment of peptic ulcer. It may also be used to prevent nausea, vomiting, and motion sickness.

Mechanism of action

Pirenzepine is a muscarinic receptor antagonist and binds to the muscarinic acetylcholine receptor. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
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
PathwayCategory
Pirenzepine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Pirenzepine can be decreased when used in combination with 1,10-Phenanthroline.
AclidiniumThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Agmatine.
Ajulemic acidThe risk or severity of Tachycardia and drowsiness can be increased when Pirenzepine is combined with Ajulemic acid.
AlcuroniumThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Alcuronium.
AlfentanilThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Alfentanil.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Alphacetylmethadol.
AlphaprodineThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Alphaprodine.
Aluminum sulfateThe therapeutic efficacy of Aluminum sulfate can be decreased when used in combination with Pirenzepine.
AmantadineThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Amantadine.
Food Interactions
  • Take 30 minutes before breakfast and at bedtime.

References

General References
  1. Czepita D: [Fundamentals of modern treatment of myopia]. Ann Acad Med Stetin. 2005;51(2):5-9. [PubMed:16519089]
External Links
Human Metabolome Database
HMDB0014808
KEGG Compound
C07508
PubChem Compound
4848
PubChem Substance
46509029
ChemSpider
4682
BindingDB
39341
ChEBI
8247
ChEMBL
CHEMBL9967
Therapeutic Targets Database
DAP000492
PharmGKB
PA10159
Wikipedia
Pirenzepine
ATC Codes
A02BX03 — Pirenzepine
MSDS
Download (36.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0.6Not Available
Caco2 permeability-6.36ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.682 mg/mLALOGPS
logP1.26ALOGPS
logP0.85ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)9.57ChemAxon
pKa (Strongest Basic)7.59ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.78 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity100.93 m3·mol-1ChemAxon
Polarizability37.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9917
Blood Brain Barrier+0.9737
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8101
P-glycoprotein inhibitor IInhibitor0.5362
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterInhibitor0.5983
CYP450 2C9 substrateNon-substrate0.7426
CYP450 2D6 substrateNon-substrate0.5571
CYP450 3A4 substrateSubstrate0.6503
CYP450 1A2 substrateInhibitor0.5788
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.8814
CYP450 3A4 inhibitorNon-inhibitor0.8958
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.5
CarcinogenicityNon-carcinogens0.946
BiodegradationNot ready biodegradable0.9839
Rat acute toxicity1.8779 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6797
hERG inhibition (predictor II)Non-inhibitor0.5475
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 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Pyridodiazepines / Alpha amino acids and derivatives / N-piperazineacetamides / N-methylpiperazines / Benzenoids / Pyridines and derivatives / Imidolactams / Tertiary carboxylic acid amides / Cyclic carboximidic acids / Heteroaromatic compounds
show 7 more
Substituents
Pyrido-para-diazepine / 1,4-benzodiazepine / Alpha-amino acid or derivatives / N-piperazineacetamide / N-methylpiperazine / N-alkylpiperazine / 1,4-diazinane / Piperazine / Pyridine / Imidolactam
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
pyridobenzodiazepine (CHEBI:8247)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Pedretti RF, Prete G, Foreman RD, Adamson PB, Vanoli E: Autonomic modulation during acute myocardial ischemia by low-dose pirenzepine in conscious dogs with a healed myocardial infarction: a comparison with beta-adrenergic blockade. J Cardiovasc Pharmacol. 2003 May;41(5):671-7. [PubMed:12717096]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:45