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Identification
- Summary
Pinaverium is a spasmolytic agent used for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract.
- Brand Names
- Dicetel
- Generic Name
- Pinaverium
- DrugBank Accession Number
- DB09090
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Pinaverium (DB09090)
- Weight
- Average: 511.52
Monoisotopic: 510.221348 - Chemical Formula
- C26H41BrNO4
- Synonyms
- Not Available
Pharmacology
- Indication
Pinaverium is indicated for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of Flatulence Combination Product in combination with: Dimethicone (DB11074) •••••••••••• •••••••• •••••• Symptomatic treatment of Irritable bowel syndrome •••••••••••• Symptomatic treatment of Irritable bowel syndrome •••••••••••• Symptomatic treatment of Functional disorders of the biliary tract •••••••••••• Used in combination for symptomatic treatment of Stomach cramps Combination Product in combination with: Dimethicone (DB11074) •••••••••••• •••••••• •••••• - Contraindications & Blackbox Warnings
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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
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- 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 Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Pinaverium can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Pinaverium is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Pinaverium. 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. - Food Interactions
- Take with a full glass of water.
- Take with food. This helps prevent pinaverium from irritating the esophagus.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Pinaverium bromide 7SCF54H12J 53251-94-8 IKGXLCMLVINENI-UHFFFAOYSA-M - 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)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dicetel Tablet 50 mg Oral Bgp Pharma Ulc 1993-12-31 Not applicable Canada 
Dicetel Tablet 100 mg Oral Bgp Pharma Ulc 1999-07-05 Not applicable Canada Pinaverium Tablet 100 mg Oral Aa Pharma Inc 2018-09-13 Not applicable Canada Pinaverium Tablet 50 mg Oral Aa Pharma Inc 2018-09-13 Not applicable Canada Truemed Group LLC Tablet 100 mg/100mg Oral Truemed Group LLC 2022-09-17 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ALEVIAN DUO ® CAPSULAS Pinaverium bromide (100 mg) + Simethicone (300 mg) Capsule, liquid filled Oral ADIUM SAS 2011-05-03 Not applicable Colombia 
BROMUX D® 100/300 MG CÁPSULA. Pinaverium bromide (100 mg) + Simethicone (300 mg) Capsule, coated Oral CLARIPACK S.A. 2015-05-26 Not applicable Colombia DICETEL® DUO Pinaverium bromide (100 mg) + Simethicone (300 mg) Tablet, coated Oral 2016-06-15 Not applicable Colombia DISPAX ® CAPSULAS DURAS CON CONTENIDO LIQUIDO Pinaverium bromide (100 mg) + Simethicone (300 mg) Capsule, coated Oral C.I. FARMACAPSULAS S.A.S. - PLANTA NO. 2 2016-11-16 Not applicable Colombia DUOTRYNE® Pinaverium bromide (100 mg) + Simethicone (300 mg) Capsule, liquid filled Oral LABORATORIOS CHALVER DE COLOMBIA S.A.S 2023-02-21 Not applicable Colombia
Categories
- ATC Codes
- A03AX04 — Pinaverium
- Drug 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
- Chemical TaxonomyProvided by Classyfire
- 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
- Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Aromatic monoterpenoid / Aryl bromide / Aryl halide / Azacycle / Benzenoid show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- U2368VVE7O
- CAS number
- 59995-65-2
- 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
References
- General References
- Christen MO: Action of pinaverium bromide, a calcium-antagonist, on gastrointestinal motility disorders. Gen Pharmacol. 1990;21(6):821-5. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Itoh Z, Takahashi I: Inhibitory effect of pinaverium bromide on gastrointestinal contractile activity in conscious dogs. Arzneimittelforschung. 1981;31(9):1450-3. [Article]
- 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. [Article]
- 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
- 33724
- ChEBI
- 135811
- ChEMBL
- CHEMBL1909324
- Wikipedia
- Pinaverium_bromide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Unknown Status Treatment Irritable Bowel Syndrome (IBS) 2 somestatus stop reason just information to hide 4 Completed Diagnostic Cancer 1 somestatus stop reason just information to hide 4 Unknown Status Treatment Sphincter of Oddi Dysfunction 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, liquid filled Oral Tablet Oral 50.000 mg Tablet Oral 100.0 mg Capsule Tablet Oral 100 mg Tablet Oral 50 mg Tablet, coated Oral 50 mg Tablet, film coated Oral 100 MG Tablet Oral Tablet, coated Oral Capsule, coated Oral Tablet Oral 100.000 mg Capsule Oral Tablet, film coated Oral 50 mg Tablet, coated Oral 100 mg Tablet Oral 100.00 mg Tablet Oral 100 mg/100mg - 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
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 209.61043 predictedDeepCCS 1.0 (2019) [M+H]+ 211.96846 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.27618 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group
- Specific Function
- Calmodulin binding
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- 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 September 15, 2015 21:22 / Updated at May 03, 2024 10:14