Oxitropium Bromide

Oxitropium bromide is an mAChR antagonist used as an anticholinergic bronchodilator drug for the treatment of asthma and chronic obstructive pulmonary disease.

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Inflammation/Immunology

mAChR[1]

Oxitropium bromide is a muscarinic antagonist which blocks musucarinic acetylcholine receptors (mAChR). Incubation with oxitropium bromide of untreated diaphragm muscle and diaphragm muscle injected with endotoxin does not increase the force-frequency curves dose-dependently in vitro; however, it causes both types of muscle to be fatigue resistant[1].

Oxitropium bromide inhalation shifts force-frequency curves upward at 2 h after inhalation and inhibits the decrease of force-frequency curves due to endotoxin injection in vivo[1]. Oxitropium bromide strongly and persistently inhibits the acetylcholine (ACh)-induced resistance. The increase in resistance induced by histamine, serotonin, leukotriene D4 or antigen is prevented by oxitropium bromide oxitropium bromide[2]. Inhalation of the anticholinergic agent oxitropium bromide at doses of 1.5 μg and higher greatly attenuates the decrease in mucus score produced by intravenous histamine but not by inhaled histamine[3].

Mice: In the oxitropium bromide inhalation group, animals are given 2 puffs of inhalation from a oxitropium bromide MDI (metered dose inhaler) via a 75-mL spacer, and then diaphragm muscles are dissected and measured as to contractility immediately, 1 hour, 2 hours and 4 hours later (n=5 animals each). An animal is placed in a centrifugal tube (inner diameter=30 mm) with a round hole (diameter=10 mm) in the bottom, its nose and mouth being exposed through the hole to breath. An oxitropium bromide MDI (metered dose inhaler) releases 2 puffs into a spacer attached to the tube. Aerosols of oxitropium bromide are inhaled for about 10 seconds, while the animal is breathing spontaneously through the hole of the tube[1].

[1]. Shindoh C, et al. Effects of inhalation or incubation of oxitropium bromide on diaphragm muscle contractility in mice. Allergol Int. 2011 Sep;60(3):365-72.

[2]. Kohno SW, et al. Effect of oxitropium bromide (Ba253) on increased airway resistance induced by various agonists and antigen in the guinea pig. Jpn J Pharmacol. 1989 Aug;50(4):455-66.

[3]. Takeyama K, et al. Effect of oxitropium bromide on histamine-induced airway goblet cell secretion. Am J Respir Crit Care Med. 1996 Jul;154(1):231-6.

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

MOLECULAR FORMULA :

C19-H26-N-O4.Br

MOLECULAR WEIGHT :

412.37

WISWESSER LINE NOTATION :

T C356 A AK DOTJ A2 A1 HOVYR&1Q &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 :

2250 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

19 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 36,353,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1150 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

25700 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

40 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 36,353,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>8 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 35,435,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

34 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 4,117,1979 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

55 gm/kg/13W-C

TOXIC EFFECTS :

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: 36,353,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

17 gm/kg/78W-C

TOXIC EFFECTS :

Gastrointestinal - decreased motility or constipation Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 36,353,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

2730 mg/kg/13W-C

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - conjunctive irritation Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 36,353,1988 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

55 gm/kg

SEX/DURATION :

male 10 week(s) pre-mating female 2 week(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 37,413,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

6600 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 37,413,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

7800 mg/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - behavioral

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 37,413,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2600 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 37,413,1989