Loperamide hydrochloride CAS 34552-83-5
Introduction：Basic information about Loperamide hydrochloride CAS 34552-83-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Loperamide hydrochloride Basic information
| Product Name: | Loperamide hydrochloride |
| Synonyms: | 4-(4-(p-chlorophenyl)-4-hydroxy-1-piperidyl)-n,n-dimethyl-2,2-diphenylbutyra;4-(p-chlorophenyl)-4-hydroxy-n,n-dimethyl-alpha,alpha-diphenyl-1-piperidine;blox;butyramidehcl;dissenten;fortasec;imodium;imosec |
| CAS: | 34552-83-5 |
| MF: | C29H34Cl2N2O2 |
| MW: | 513.5 |
| EINECS: | 252-082-4 |
| Product Categories: | IMODIUM;Other APIs;ACTIVE PHARMACEUTICAL INGREDIENTS;Intermediates & Fine Chemicals;Pharmaceuticals;Isotope Labeled Compounds;Opioid receptor and opioid-like receptor;Amines;Heterocycles;34552-83-5 |
| Mol File: | 34552-83-5.mol |
Loperamide hydrochloride Chemical Properties
| Melting point | 223-225°C |
| density | 1.1905 (rough estimate) |
| refractive index | 1.6100 (estimate) |
| storage temp. | 2-8°C |
| solubility | Slightly soluble in water, freely soluble in ethanol (96 per cent) and in methanol. |
| pka | 8.66(at 25℃) |
| form | Solid |
| color | White to Almost white |
| Merck | 14,5571 |
| Major Application | forensics and toxicology pharmaceutical (small molecule) |
| InChI | InChI=1S/C29H33ClN2O2.ClH/c1-31(2)27(33)29(24-9-5-3-6-10-24,25-11-7-4-8-12-25)19-22-32-20-17-28(34,18-21-32)23-13-15-26(30)16-14-23;/h3-16,34H,17-22H2,1-2H3;1H |
| InChIKey | PGYPOBZJRVSMDS-UHFFFAOYSA-N |
| SMILES | C(C(=O)N(C)C)(CCN1CCC(O)(C2C=CC(Cl)=CC=2)CC1)(C1=CC=CC=C1)C1=CC=CC=C1.Cl |
| CAS DataBase Reference | 34552-83-5(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 25 |
| Safety Statements | 45 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | TM4960000 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 29333990 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral |
| Toxicity | LD50 in mice (mg/kg): 75 s.c.; 28 i.p.; 105 orally; in rats (mg/kg): 185 orally (Niemegeers) |
| Chemical Properties | White Solid |
| Originator | Imodium,Janssen,UK,1975 |
| Uses | Labeled Loperamide, which is used as an antidiarrheal |
| Uses | Loperamide hydrochloride is a Ca2+ channel protein inhibitor and MOR activator. |
| Uses | Ca channel blocker |
| Definition | ChEBI: A hydrochloride obtained by combining loperamide with one equivalent of hydrochloric acid. Used for treatment of diarrhoea resulting from gastroenteritis or inflammatory bowel disease. |
| Indications | Loperamide hydrochloride (Imodium) structurallyresembles both haloperidol and meperidine. In equaldoses, loperamide protects against diarrhea longer thandoes diphenoxylate. It reduces the daily fecal volumeand decreases intestinal fluid and electrolyte loss.Loperamide produces rapid and sustained inhibition ofthe peristaltic reflex through depression of longitudinaland circular muscle activity.The drug also possesses antisecretoryactivity, presumably through an effect on intestinalopioid receptors. |
| Manufacturing Process | 23.6 parts of 2-oxo-3,3-diphenyl-tetrahydrofuranare melted at 100°C in anoil-bath and gaseous hydrogen bromide is introduced into it during 3 hours.The reaction mixture is cooled and triturated in benzene. The product isfiltered off, washed with petroleum ether and dried in an exsiccator, yielding4-bromo-2,2-diphenylbutyric acid; MP 127.5%. To a stirred suspension of 16 parts of 4-bromo-2,2-diphenylbutyric acid in 150parts of chloroform are added dropwise 16 parts of thionyl chloride and thewhole is stirred and refluxed for 2 hours. The reaction mixture is evaporated,yielding 4-bromo-2,2-diphenyl-butyrylchloride as a residue. 60 parts of 4-bromo-2,2-diphenylbutyrylchloride are dissolved in 400 parts oftoluene and gaseous dimethylamine is introduced slowly into the solutionwhile cooling (temperature is kept at about 0°C). The introduction is ceasedwhen dimethylamine escapes from the cooler, and stirring is continued for 2hours at ordinary temperature. The precipitated product is filtered off anddissolved in a minimum quantity of water. The product is extracted withchloroform. The extract is dried and evaporated. The residue solidifies ontriturating in 4-methyl-2-pentanone. The solid is filtered off and dried, yieldingdimethyl -(tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide; MP 169°to 171.5°C. A mixture of 6.33 parts of 4-(p-chlorophenyl)-4-piperidinol, 8 parts of sodiumcarbonate, 0.2 part of potassium iodide and 240 parts of 4-methyl-2-pentanone is distilled azeotropically. Then there are added 12.12 parts ofdimethyl-(tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide (from thepreceding step) and the whole is stirred and refluxed for about 15 hours. Thereaction mixture is filtered hot and the filtrate is evaporated. The oily residue is dissolved in 2-propanol and to this solution is added anexcess of 2-propanol previously saturated with gaseous hydrogen chloride.The whole is evaporated and the oily residue is warmed in diluted hydrochloricacid solution. Upon the addition of toluene, the salt is precipitated. It isfiltered off, boiled in acetone, and filtered off again after cooling, yielding 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-α,α-diphenylpiperidine-1-butyramidehydrochloride; MP 222.1°C. |
| Brand name | Imodium (Janssen);Imodium (McNeil). |
| Therapeutic Function | Antidiarrheal |
| General Description | Loperamide is an antidiarrheal agent used in controlling acute nonspecific diarrhea and chronic diarrhea associated with inflammatory bowel diseases. |
| Biological Activity | High affinity μ -opioid receptor agonist with peripheral selectivity (K i values are 2, 48 and 1156 nM for μ -, δ - and κ -opioid receptors respectively). Antidiarrhoeal and antihyperalgesic agent. Also a Ca 2+ channel blocker; at low micromolar concentrations it blocks broad spectrum neuronal HVA Ca 2+ channels and at higher concentrations it reduces Ca 2+ flux through NMDA receptor operated channels. |
| Biochem/physiol Actions | Loperamide hydrochloride (HCl) is a non-selective Ca2+ channel blocker. At nanomolar concentrations, it binds to μ-opioid receptors. Loperamide HCl does not cross the blood-brain barrier. |
| Mechanism of action | Loperamide also is a potent inhibitor of intestinal CYP3A4, increasing the intestinal absorption ofother CYP3A4 substrates. The clinically significant drug interactions of loperamide withcoadministered CYP3A4 and CYP2C8 substrates or inhibitors would be limited, however, becauseof its two metabolic pathways. |
| Pharmacokinetics | Loperamide ismarketed as capsules (2 mg) and liquid (1 mg/5 mL) preparations. The recommended dose is 4 mginitially and an additional 2 mg following each diarrheal stool. The dose should not exceed 16mg/day. It is too lipophilic to dissolve in water for an intravenous dosage form, a property that limitsits abuse potential. The compound is highly lipophilic and undergoes slow dissolution, thus limitingthe bioavailability of the agent to approximately 40% of the dose. Its low oral bioavailability alsocan be attributed to first-pass metabolism by both CYP2C8 and CYP3A4 to its primary N-demethylmetabolite. Peak plasma levels are reached in approximately 5 hours, with an elimination half-lifeof approximately 11 hours. Approximately 1% of the dose is excreted into the urine unchanged. |
| Clinical Use | Loperamide is effectiveagainst a wide range of secretory stimuli and can beused in the control and symptomatic relief of acute diarrheathat is not secondary to bacterial infection. |
| Side effects | Adverse effects associated with its use include abdominalpain and distention, constipation, dry mouth, hypersensitivity,and nausea and vomiting. |
| storage | Room temperature |
Loperamide hydrochloride Preparation Products And Raw materials
| Raw materials | Thionyl chloride-->Dimethylamine-->Hydrochloric acid-->Hydrogen bromide-->4-(4-Chlorophenyl)piperidin-4-ol |
