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Details

Stereochemistry RACEMIC
Molecular Formula C19H28NO3.Br
Molecular Weight 398.335
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLYCOPYRROLATE

SMILES

[Br-].C[N+]1(C)CC[C@@H](C1)OC(=O)[C@@](O)(C2CCCC2)C3=CC=CC=C3

InChI

InChIKey=VPNYRYCIDCJBOM-QQTWVUFVSA-M
InChI=1S/C19H28NO3.BrH/c1-20(2)13-12-17(14-20)23-18(21)19(22,16-10-6-7-11-16)15-8-4-3-5-9-15;/h3-5,8-9,16-17,22H,6-7,10-14H2,1-2H3;1H/q+1;/p-1/t17-,19-;/m0./s1

HIDE SMILES / InChI

Description

Glycopyrrolate is a synthetic anticholinergic agent with a quaternary ammonium structure. Glycopyrrolate is a muscarinic competitive antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics. Glycopyrrolate binds competitively to the muscarinic acetylcholine receptor. Like other anticholinergic (antimuscarinic) agents, it inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of smooth muscle, cardiac muscle, the sinoatrial node, the atrioventricular node, exocrine glands and, to a limited degree, in the autonomic ganglia. Thus, it diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions. Glycopyrrolate antagonizes muscarinic symptoms (e.g., bronchorrhea, bronchospasm, bradycardia, and intestinal hypermotility) induced by cholinergic drugs such as the anticholinesterases. The highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes, such as the blood-brain barrier, in contrast to atropine sulfate and scopolamine hydrobromide, which are highly non-polar tertiary amines which penetrate lipid barriers easily. Glycopyrrolate is marketed under the brand names Robinul, Robinul Forte, Cuvposa. In October 2015, glycopyrrolate was approved by the FDA for use as a standalone treatment for Chronic obstructive pulmonary disease (COPD), as Seebri Neohaler.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
9.9 null [pIC50]
9.3 null [pIC50]
9.6 null [pIC50]
9.8 null [pIC50]
9.7 null [pIC50]
9.9 null [pIC50]
9.3 null [pIC50]
9.6 null [pIC50]
9.8 null [pIC50]
9.7 null [pIC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ROBINUL
Primary
SEEBRI NEOHALER

Cmax

ValueDoseCo-administeredAnalytePopulation
0.08 ng/mL
2.4 % 1 times / day multiple, topical
GLYCOPYRRONIUM plasma
Homo sapiens
3.47 μg/L
8 μg/kg bw single, intravenous
GLYCOPYRRONIUM plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
0.88 ng × h/mL
2.4 % 1 times / day multiple, topical
GLYCOPYRRONIUM plasma
Homo sapiens
6.64 μg × h/L
8 μg/kg bw single, intravenous
GLYCOPYRRONIUM plasma
Homo sapiens
8.64 μg × h/L
6 μg/kg bw single, intravenous
GLYCOPYRRONIUM plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
0.83 h
6 μg/kg bw single, intravenous
GLYCOPYRRONIUM plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
68.3%
GLYCOPYRRONIUM plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Anesthesia Preanesthetic (reduction of secretions): 0.004 mg (0.02 mL)/kg IM 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered. Intraoperative: 0.1 mg (0.5 mL) IV repeated as needed every 2 to 3 minutes. Reversal of neuromuscular blockade: 0.2 mg (1.0 mL) IV for each 1.0 mg of neostigmine or 5 mg of pyridostigmine. Reversal of bradycardia, vagal reflexes (intraoperative): 0.1 mg IV repeated as needed at 2 to 3 minute intervals. Usual Adult Dose for Peptic Ulcer Parenteral: 0.1 mg (0.5 mL) IV or IM every 4 hours, 3 to 4 times daily. If a more profound effect is required the dose may be increased to 0.2 mg (1 mL). 1 mg oral tablet: Initial dose: 1 mg orally 3 times daily or 1 mg in the morning, 1 mg in the early afternoon, and 2 mg at bedtime. Maintenance dose: 1 mg orally twice daily to a maximum of 8 mg per day. 2 mg oral tablet: 2 mg orally 2 to 3 times daily to a maximum of 8 mg per day. 1.5 mg oral tablet: Used to provide intermediate titration doses based on patient response. Usual Pediatric Dose for Anesthesia Preanesthetic: 0.004 mg (0.02 mL)/kg IM 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered. Children under 2 years of age may require up to 0.009 mg (0.45 mL)/kg. Intraoperative: 0.004 mg (0.02 mL)/kg IV not to exceed 0.1 mg (0.5 mL) in a single dose, repeated as needed every 2 to 3 minutes. Reversal of neuromuscular blockade: 0.4 mg (2 mL)/kg IV for each 1 mg of neostigmine or 5 mg of pyridostigmine. Reversal of bradycardia, vagal reflexes (intraoperative): 4 mcg/kg/dose IV (maximum dose: 100 mcg/dose) at 2 to 3 minute intervals. Usual Pediatric Dose for Excessive Salivation 3 years to 16 years with neurologic conditions associated with problem drooling: Initiate dosing at 0.02 mg/kg orally three times daily and titrate in increments of 0.02 mg/kg every 5 to 7 days, based on therapeutic response and adverse reactions. Maximum recommended dose is 0.1 mg/kg three times daily, not to exceed 1.5 to 3 mg per dose based upon weight. Administer at least one hour before or two hours after meals.
Route of Administration: Other
In Vitro Use Guide
Glycopyrrolate inhibited contraction induced by EFS (40 V, 0.5 ms, 4 Hz for 15 s every 4 min) in guinea-pig trachea in a concentration-dependent manner (IC50=0.15 nM, n=5 ± 12). Glycopyrrolate inhibited contraction induced by EFS (40 V, 0.5 ms, 8 Hz for 15 s every 4 min) in human trachea in a concentration-dependent manner (IC50=0.44 nM, n=3 ± 8).