596-51-0 Usage
Description
Glycopyrrolate, also known as 3-hydroxy-1,1-dimethylpyrrolidinium bromide-cyclopentylmandelate (Robinul), is a quaternary ammonium salt that occurs as a white, crystalline powder. It is soluble in water or alcohol but practically insoluble in chloroform or ether. Glycopyrrolate is a typical anticholinergic drug, possessing atropine-like effects at adequate dosage levels. It has a spasmolytic effect on the musculature of the gastrointestinal and genitourinary tracts, reduces gastric and pancreatic secretions, and decreases the quantity of perspiration and saliva. Its side effects are also typically atropine-like, including dryness of the mouth, urinary retention, blurred vision, and constipation. Glycopyrrolate is a more potent antagonist on M1 than on M2 and M3 receptors, and its low affinity for M2 receptors may explain the low incidence of tachycardia during its use as an antispasmodic. Due to its quaternary ammonium character, glycopyrrolate rarely causes CNS disturbances, although in sufficiently high dosage, it can bring about ganglionic and myoneural junction block.
Uses
Used in Pharmaceutical Industry:
Glycopyrrolate is used as an antispasmodic for the treatment of air flow blockage and prevention of worsening chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is also used as a preoperative antimuscarinic to reduce salivary, tracheobronchial, and pharyngeal secretions, to reduce the volume and free acidity of gastric secretions, and to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation.
Used in Medical Applications:
Glycopyrrolate is used as a treatment for sialorrhea, peptic ulcers, and chronic obstructive pulmonary disease (COPD). Formulations containing glycopyrrolate have been developed to target these conditions effectively.
Used in Preoperative Medication:
Glycopyrrolate is used as a preoperative medication to reduce secretions and block cardiac vagal inhibitory reflexes, ensuring a smoother induction of anesthesia and intubation process.
Used in Treatment of Sialorrhea:
Glycopyrrolate is used as a treatment for sialorrhea, a condition characterized by excessive saliva production, by inhibiting salivation in a rat model of sialorrhea induced by pilocarpine.
Used in Treatment of Peptic Ulcers:
Glycopyrrolate is used in the treatment of peptic ulcers by reducing post-prandial gastric antral motility in dogs when administered at a dose of 0.01 mg/kg.
Used in Treatment of Chronic Obstructive Pulmonary Disease (COPD):
Glycopyrrolate is used in the treatment of COPD, a long-term lung disease that causes bronchospasm (difficulty with breathing), by inducing relaxation of precontracted isolated human bronchi when used at concentrations of 0.01, 0.1, or 1 μM.
Originator
Robinul,Robins,US,1961
Manufacturing Process
A mixture of 42.5 grams (0.17 mol) of methyl α-cyclopentyl mandelate and 18
grams (0.175 mol) of 1-methyl-3-pyrrolidinol in 500 ml of heptane was
refluxed under a Dean and Stark moisture trap, with the addition of four 0.1
gram pieces of sodium at 1-hour intervals. After 5 hours' refluxing the
solution was concentrated to one-half volume, and extracted with cold 3N HCl.
The acid extract was made alkaline with aqueous sodium hydroxide and
extracted with ether which was washed, dried over sodium sulfate, filtered
and concentrated. The residue was fractionated at reduced pressure. Yield 33
grams (64%); BP 151° to 154°C/0.2 mm, nD23= 1.5265.
The hydrochloride salt was precipitated as an oil from an ethereal solution of
the base with ethereal hydrogen chloride. It was crystallized from butanone;
MP 170° to 171.5°C.
The methyl bromide quaternary was prepared by saturating a solution of the
base in dry ethyl acetate with methyl bromide. After standing for 9 days the resulting crystalline solid was filtered and recrystallized from butanone and
from ethyl acetate; MP 193° to 194.5°C.
Therapeutic Function
Spasmolytic
Biochem/physiol Actions
Glycopyrrolate is long-acting muscarinic antagonist (LAMA). It is kinetically selective muscarinic M3 receptor antagonist.
Mechanism of action
Glycopyrrolate exhibits onset of action within 1 minute when given intravenously and an elimination half-life of approximately 50 minutes. Glycopyrrolate undergoes urinary excretion and elimination.
Clinical Use
Glycopyrrolate is used as an adjunct in the management of pepticulcer and other GI ailments associated with hyperacidity,hypermotility, and spasm. In common with other anticholinergics,its use does not preclude dietary restrictions or use ofantacids and sedatives if these are indicated.
Side effects
dry mouthblurred visionvision problemsloss of tasteheadachenervousnessconfusiondrowsiness
Safety Profile
Poison by intravenous
and intraperitoneal routes. Moderately toxic
by ingestion and subcutaneous routes.
Experimental reproductive effects. When
heated to decomposition it emits very toxic
fumes of NOx and Br-. See also BROMIDES.
Veterinary Drugs and Treatments
Glycopyrrolate injection is approved for use in dogs and cats. The
FDA approved
indication for these species is as a preanesthetic anticholinergic
agent. The drug is also used to treat sinus bradycardia,
sinoatrial arrest, and incomplete AV block, where anticholinergic
therapy may be beneficial. When cholinergic agents such as neostigmine
or pyridostigmine are used to reverse neuromuscular
blockade
due to non-depolarizing muscle relaxants, glycopyrrolate may
be administered simultaneously
to prevent the peripheral muscarinic
effects of the cholinergic agent.
Check Digit Verification of cas no
The CAS Registry Mumber 596-51-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,9 and 6 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 596-51:
(5*5)+(4*9)+(3*6)+(2*5)+(1*1)=90
90 % 10 = 0
So 596-51-0 is a valid CAS Registry Number.
InChI:InChI=1/C20H30NO3.BrH/c1-21(2)13-12-18(15-21)24-19(22)14-20(23,17-10-6-7-11-17)16-8-4-3-5-9-16;/h3-5,8-9,17-18,23H,6-7,10-15H2,1-2H3;1H/q+1;/p-1
596-51-0Relevant articles and documents
Glycopyrronium bromide intermediate as well as preparation method and application thereof
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Paragraph 0078-0100, (2022/01/10)
The invention provides a glycopyrronium bromide intermediate as well as a preparation method and application thereof, and relates to the technical field of chemical synthesis. The preparation method of the glycopyrronium bromide intermediate comprises the step of carrying out transesterification reaction on methyl alpha-cyclopentyl mandelate as a raw material and 1, 4-dibromo-2-butanol under the action of a first base catalyst to obtain a glycopyrronium bromide intermediate, namely a compound 2. The preparation method of glycopyrronium bromide comprises the step of carrying out quaternization reaction on the compound 2 and dimethylamine under the action of a second base catalyst to obtain glycopyrronium bromide. The method has the advantages of cheap and easily available raw materials, avoidance of use of toxic gas bromomethane commonly used in the prior art, small environmental pollution, environment-friendliness, mild reaction conditions, easy control of the reaction process, avoidance of use of metal sodium, safe operation, high safety coefficient, great reduction of the reaction steps, production cost saving, high product yield, and high purity. A process route capable of industrially producing products with higher quality is provided.
PROCESS FOR SYNTHESIS OF GLYCOPYRRONIUM BROMIDE
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, (2018/09/26)
Provided herein are processes for preparation of glycopyrronium bromide comprising reaction of N-methylpyrrolidin-3-ol with compounds of Formula I or Formula II followed by additional steps.
Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists
Xiang, Zuojuan,Liu, Jun,Sun, Hongbin,Wen, Xiaoan
, p. 1173 - 1182 (2017/08/15)
The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.