Identification
- Name
- Pinaverium
- Accession Number
- DB09090
- Type
- Small Molecule
- Groups
- Approved
- Description
Pinaverium is a spasmolytic agent used for functional gastrointestinal disorders. It is a quaternary ammonium compound that acts as an atypical calcium antagonist to restore normal bowel function. It is shown to relieve GI spasm and pain, transit disturbances and other symptoms related to motility disorders 1 and may be considered as effective first-lline therapy for patients with irritable bowel syndrome (IBS) 5. Pinaverium bromide is the common ingredient in formulations, mostly as oral tablets. Although it is not a currently approved drug by the FDA, pinaverium is available in over 60 countries including Canada.
- Structure
Structure for Pinaverium (DB09090)
- Synonyms
- Not Available
- Product Ingredients
Ingredient UNII CAS InChI Key Pinaverium bromide 7SCF54H12J 53251-94-8 IKGXLCMLVINENI-UHFFFAOYSA-M - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataDicetel Tablet Oral Bgp Pharma Ulc 1999-07-05 Not applicable Canada 
Dicetel Tablet Oral Bgp Pharma Ulc 1993-12-31 Not applicable Canada Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataApo-pinaverium Tablet Oral Apotex Corporation 2018-09-13 Not applicable Canada Apo-pinaverium Tablet Oral Apotex Corporation 2018-09-13 Not applicable Canada Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- International/Other Brands
- Alevian Duo (Takeda) / Blocafer (Liferpal, Mexico) / Delibs (CONMED, Taiwan) / Ilyang Dicetel (Ilyang) / Nulite (Dominguez, Argentina) / Pakab (Wermar, Mexico) / Pinar (ABL Pharma, Peru) / Pinaven (Johnson, Taiwan) / Pladuet (Interlab Pharmaceutica, Mexico) / Planex (Rimsa, Mexico) / Riginal (Royal Pharma, Chile) / Spascolon (Chemi ph, Egypt) / Spasmopinaver (GNP, Egypt) / Spastec (Swiss Pharm, Taiwan) / Sucam (Everest, Taiwan) / Zerpyco (Atlantis, Mexico)
- Categories
- Agents causing hyperkalemia
- Alimentary Tract and Metabolism
- Antiarrhythmic agents
- Autonomic Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs for Functional Gastrointestinal Disorders
- Membrane Transport Modulators
- Miscellaneous GI Drugs
- Oxazines
- Parasympatholytics
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Vasodilating Agents
- UNII
- U2368VVE7O
- CAS number
- 59995-65-2
- Weight
- Average: 511.52
Monoisotopic: 510.221348 - Chemical Formula
- C26H41BrNO4
- InChI Key
- DDHUTBKXLWCZCO-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H41BrNO4/c1-26(2)21-6-5-19(22(26)16-21)7-11-31-12-8-28(9-13-32-14-10-28)18-20-15-24(29-3)25(30-4)17-23(20)27/h15,17,19,21-22H,5-14,16,18H2,1-4H3/q+1
- IUPAC Name
- 4-[(2-bromo-4,5-dimethoxyphenyl)methyl]-4-[2-(2-{6,6-dimethylbicyclo[3.1.1]heptan-2-yl}ethoxy)ethyl]morpholin-4-ium
- SMILES
- COC1=C(OC)C=C(C[N+]2(CCOCCC3CCC4CC3C4(C)C)CCOCC2)C(Br)=C1
Pharmacology
- Indication
Pinaverium is indicated for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract.
- Associated Conditions
- Pharmacodynamics
Pinaverium is a selective and specific voltage-dependent calcium channel blocker located on intestinal smooth muscle cells to inhibit calcium influx. It mediates various effects on the GI tract: it causes oesophageal, gastric and duodenal relaxation, relaxes the colon and intestines, inhibits colonic motility in response to food, hormonal or pharmacological stimuli, accelerates gastric emptying, and reduces contractions of the gallbladder and phasic contractions of sphincter of Oddi 10,5. At higher concentrations, pinaverium also exhibits very weak anticholinergic effects 10 but is not shown to display vasodilatory or anti-arrythmic actions 9.
- Mechanism of action
Pinaverium interacts with the 1,4-dihydropyridine binding sites on voltage dependent L-type calcium channels located on GI smooth muscle cells in a competitve manner 2. The binding site is located in the alpha 1S subunit and pinaverium most likely antagonizes the action of calcium ions by stabilizing a non-conducting channel state 8. Pinaverium inhibits smooth muscle contractions of the GI tract by inhibiting inward calcium current and calcium influx. It is suggested that pinaverium may be able to bind to both closed or inactivates states of the calcium channel with similar affinity 9,1.
Target Actions Organism AVoltage-dependent L-type calcium channel subunit alpha-1S antagonistinhibitorHumans - Absorption
After oral administration, pinaverium is poorly absorbed (5-10%) followed by uptake by liver. Poor absorption is due to its highly polar quaternary ammonium group and high molecular weight 10, which limits extensive diffusion across all cell membranes and promotes its selectivity towards the gastrointestinal tracts []. Peak plasma concentration is reached within one hour after administration and the absolute oral bioavailability is reported to be less than 1%.
- Volume of distribution
It is selectively distributed to the digestive tract due to poor absorption and marked hepatobiliary excretion 10.
- Protein binding
Pinaverium is highly bound to human plasma proteins with the ratio of 97% 10.
- Metabolism
Hepatic metabolism of pinaverium involves demethylation of one of the methoxy groups, hydroxylation of the norpinanyl ring and elimination of the benzyl group with subsequent opening of the morpholine ring 10.
- Route of elimination
Pinaverium is predominantly eliminated into feces 10.
- Half life
The mean elimination half life is approximately 1.5 hours 10.
- Clearance
- Not Available
- Toxicity
Some minor GI-related adverse effects include epigastric pain and/or fullness, nausea, constipation, heartburn, distension, and diarrhoea. Other side effects are headache, dry mouth, drowsiness, vertigo and skin allergy. Oral LD50 in mice, rats and rabbits are 1531 mg/kg, 1145 mg/kg and 154 mg/kg, respectively 10. Pinaverium displays no teratogenic, mutagenic or carcinogenic potential.
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn moreStructured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn moreStructured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- Drug Interactions
- 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 Unlock Additional Data2,4-thiazolidinedione The risk or severity of hypoglycemia can be increased when Pinaverium is combined with 2,4-thiazolidinedione. Abafungin The therapeutic efficacy of Abafungin can be increased when used in combination with Pinaverium. Abexinostat The risk or severity of QTc prolongation can be increased when Pinaverium is combined with Abexinostat. Acarbose The risk or severity of hypoglycemia can be increased when Pinaverium is combined with Acarbose. Acebutolol The risk or severity of bradycardia can be increased when Pinaverium is combined with Acebutolol. Aceclofenac The risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Pinaverium. Acemetacin The risk or severity of hyperkalemia can be increased when Pinaverium is combined with Acemetacin. Acepromazine The risk or severity of hypotension can be increased when Acepromazine is combined with Pinaverium. Aceprometazine The risk or severity of QTc prolongation can be increased when Pinaverium is combined with Aceprometazine. Acetohexamide The risk or severity of hypoglycemia can be increased when Pinaverium is combined with Acetohexamide. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- Food Interactions
- Take with a full glass of water.
- Take with food. This helps prevent pinaverium from irritating the esophagus.
References
- General References
- Christen MO: Action of pinaverium bromide, a calcium-antagonist, on gastrointestinal motility disorders. Gen Pharmacol. 1990;21(6):821-5. [PubMed:2177709]
- Feron O, Wibo M, Christen MO, Godfraind T: Interaction of pinaverium (a quaternary ammonium compound) with 1,4-dihydropyridine binding sites in rat ileum smooth muscle. Br J Pharmacol. 1992 Feb;105(2):480-4. [PubMed:1313732]
- Baumgartner A, Drack E, Halter F, Scheurer U: Effects of pinaverium bromide and verapamil on the motility of the rat isolated colon. Br J Pharmacol. 1985 Sep;86(1):89-94. [PubMed:4052731]
- Zheng L, Lai Y, Lu W, Li B, Fan H, Yan Z, Gong C, Wan X, Wu J, Huang D, Wang Y, Mei Y, Li Z, Jiang Z, Liu X, Ye J, Yang Y, Huang H, Xiao J: Pinaverium Reduces Symptoms of Irritable Bowel Syndrome in a Multicenter, Randomized, Controlled Trial. Clin Gastroenterol Hepatol. 2015 Jul;13(7):1285-1292.e1. doi: 10.1016/j.cgh.2015.01.015. Epub 2015 Jan 26. [PubMed:25632806]
- Bobo MH, Magous R, Christen MO, Bali JP: Effect of pinaverium and other calcium channel blockers on contraction of isolated gastric antral smooth muscle cells caused by gastrointestinal hormones. Life Sci. 1994;54(25):1947-54. [PubMed:8201843]
- Awad R, Dibildox M, Ortiz F: Irritable bowel syndrome treatment using pinaverium bromide as a calcium channel blocker. A randomized double-blind placebo-controlled trial. Acta Gastroenterol Latinoam. 1995;25(3):137-44. [PubMed:8600700]
- Itoh Z, Takahashi I: Inhibitory effect of pinaverium bromide on gastrointestinal contractile activity in conscious dogs. Arzneimittelforschung. 1981;31(9):1450-3. [PubMed:7197953]
- Tikhonov DB, Zhorov BS: Structural model for dihydropyridine binding to L-type calcium channels. J Biol Chem. 2009 Jul 10;284(28):19006-17. doi: 10.1074/jbc.M109.011296. Epub 2009 May 5. [PubMed:19416978]
- Godfraind T, Govoni S, Paoletti R, Vanhoutte PM (2013). Calcium Antagonists: Pharmacology and Clinical Research (pp. 306-307). Springer Science & Business Media. [ISBN:940111725X]
- BGP Pharma ULC: DICETEL (Pinaverium Bromide) product monograph [Link]
- External Links
- PubChem Compound
- 40704
- PubChem Substance
- 310265017
- ChemSpider
- 37182
- BindingDB
- 50101975
- RxNav
- 33724
- ChEBI
- 135811
- ChEMBL
- CHEMBL1909324
- Wikipedia
- Pinaverium
- ATC Codes
- A03AX04 — Pinaverium
- AHFS Codes
- 56:92.00 — Miscellaneous GI Drugs
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Diagnostic Malignancies 1 4 Recruiting Treatment Sphincter of Oddi Dysfunction 1 Not Available Active Not Recruiting Treatment Irritable Bowel Syndrome (IBS) 1 Not Available Unknown Status Treatment Irritable Bowel Syndrome (IBS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 152-158 Product monograph water solubility Slightly soluble Product monograph - Predicted Properties
Property Value Source Water Solubility 3.42e-06 mg/mL ALOGPS logP 3.71 ALOGPS logP 0.67 ChemAxon logS -8.2 ALOGPS pKa (Strongest Acidic) 17.16 ChemAxon pKa (Strongest Basic) -3.8 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 36.92 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 143.32 m3·mol-1 ChemAxon Polarizability 54.41 Å3 ChemAxon Number of Rings 4 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as bicyclic monoterpenoids. These are monoterpenoids containing exactly 2 rings, which are fused to each other.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Prenol lipids
- Sub Class
- Monoterpenoids
- Direct Parent
- Bicyclic monoterpenoids
- Alternative Parents
- Aromatic monoterpenoids / Dimethoxybenzenes / Phenylmethylamines / Phenoxy compounds / Anisoles / Benzylamines / Alkyl aryl ethers / Aralkylamines / Bromobenzenes / Morpholines show 10 more
- Substituents
- Aromatic monoterpenoid / Bicyclic monoterpenoid / Pinane monoterpenoid / Dimethoxybenzene / O-dimethoxybenzene / Phenoxy compound / Benzylamine / Anisole / Methoxybenzene / Phenol ether show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- 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
- CACNA1S
- Uniprot ID
- Q13698
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1S
- Molecular Weight
- 212348.1 Da
References
- Tikhonov DB, Zhorov BS: Structural model for dihydropyridine binding to L-type calcium channels. J Biol Chem. 2009 Jul 10;284(28):19006-17. doi: 10.1074/jbc.M109.011296. Epub 2009 May 5. [PubMed:19416978]
- Feron O, Wibo M, Christen MO, Godfraind T: Interaction of pinaverium (a quaternary ammonium compound) with 1,4-dihydropyridine binding sites in rat ileum smooth muscle. Br J Pharmacol. 1992 Feb;105(2):480-4. [PubMed:1313732]
Enzymes
- 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. [PubMed:22039822]
Drug created on September 15, 2015 15:22 / Updated on May 30, 2020 00:22
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