Glycopyrrolate

Glycopyrrolate(Glycopyrronium Br) is a muscarinic competitive antagonist used as an antispasmodic.IC50 Value:Target: mAChR (Muscarinic acetylcholine receptor M1)in vitro: Glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide [1].in vivo: Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week six and 4 days of week seven when the daily dose was reduced to two tablets for 3 days. glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken [2]. Glycopyrrolate has a slow and erratic absorption from the gastrointestinal system, but even low plasma levels are associated with a distinct and long-lasting antisialogic effect [3]. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children [4]. phase III study, 52.3% of glycopyrrolate oral solution recipients (aged 3-18 years; n = 137) had an mTDS response (primary endpoint); the response rate was consistently above 50% at all 4-weekly timepoints, aside from the first assessment at week 4 (40.3%). In general, glycopyrrolate oral solution was well tolerated in clinical trials. The majority of adverse events were within expectations as characteristic anticholinergic outcomes [5].Toxicity: Side effects include dry mouth, difficult urinating, heachaches, diarrhea and constipation. The medication also induces drowsiness or blurred vision. LD50=709 mg/kg (rat, oral).

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[1]. Haddad, E.B., et al., Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways. Br J Pharmacol, 1999. 127(2): p. 413-20.

[2]. Neverlien, P.O., et al., Glycopyrrolate treatment of drooling in an adult male patient with cerebral palsy. Clin Exp Pharmacol Physiol, 2000. 27(4): p. 320-2.

[3]. Olsen, A.K. and P. Sjogren, Oral glycopyrrolate alleviates drooling in a patient with tongue cancer. J Pain Symptom Manage, 1999. 18(4): p. 300-2.

[4]. Kumar, M.G., et al., Oral Glycopyrrolate for Refractory Pediatric and Adolescent Hyperhidrosis. Pediatr Dermatol, 2013.

[5]. Garnock-Jones, K.P., Glycopyrrolate oral solution: for chronic, severe drooling in pediatric patients with neurologic conditions. Paediatr Drugs, 2012. 14(4): p. 263-9.

Carbachol | Darifenacin HBr | Arecoline hydrobromide | Pirenzepine, Dihydrochloride | Imidafenacin | Benztropine Mesylate | Xanomeline oxalate | Batefenterol | Bethanechol chloride | Cevimeline hydrochloride hemihydrate | Otilonium Bromide | solifenacin | VU0467154 | Anisodamine | Hyoscyamine

MOLECULAR FORMULA :

C19-H28-N-O3.Br

MOLECULAR WEIGHT :

398.39

WISWESSER LINE NOTATION :

T5KTJ A1 A1 COVXQR&- AL5TJ &E

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

709 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,93,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

196 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 17,361,1970

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

833 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,627,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

570 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

JMPCAS Journal of Medicinal and Pharmaceutical Chemistry. (Washington, DC) V.1-5, 1959-62. For publisher information, see JMCMAR. Volume(issue)/page/year: 2,523,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

90 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

JMPCAS Journal of Medicinal and Pharmaceutical Chemistry. (Washington, DC) V.1-5, 1959-62. For publisher information, see JMCMAR. Volume(issue)/page/year: 2,523,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

122 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 26,741,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

15 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

29ZVAB "Handbook of Analytical Toxicology," Sunshine, I., ed., Cleveland, OH, Chemical Rubber Co., 1969 Volume(issue)/page/year: -,55,1969

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

2360 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,627,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

29100 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,627,1973 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6600 mg/kg/30D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - inflammation, necrosis, or scarring of bladder Endocrine - changes in adrenal weight Blood - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,627,1973

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18 gm/kg/26W-C

TOXIC EFFECTS :

Endocrine - changes in adrenal weight Endocrine - changes in thyroid weight Blood - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,627,1973 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 mg/kg

SEX/DURATION :

lactating female 1 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,721,1978 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6055 No. of Facilities: 85 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 5770 (estimated) No. of Female Employees: 4866 (estimated)