Ipratropium bromide

Names

[ Name ]:
Ipratropium bromide

[Synonym ]:
(8r)-3a-Hydroxy-8-isopropyl-1aH,5aH-tropanium Bromide (±)Tropate
Ipratropium
Ipratropium bromide
ATEM
Ipratropium (bromide)
ipratropiumbromid
MFCD00069291
Ipraxa
N-Isopropylnoratropinium bromomethylate
Rinatec
Atrovent forte
Apovent
Narilet
Itrop
(3-endo,8-syn)-3-[(3-Hydroxy-2-phenylpropanoyl)oxy]-8-isopropyl-8-methyl-8-azoniabicyclo[3.2.1]octane bromide
Sch 100
pate
Aeroven
8-Azoniabicyclo[3.2.1]octane, 3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-, bromide, (3-endo,8-syn) (1:1)
Bitrop
sch1000
8-Isopropylnoratropine methobromide
Atrovent
EINECS 244-873-8

Biological Activity

[Description]:

Ipratropium Bromide is a muscarinic antagonist, bronchodilator, N-Isopropyl salt of atropine.Target: mAChRIpratropium bromide, a nonselective muscarinic antagonist, is widely prescribed for the treatment of chronic obstructive pulmonary disease (COPD). In anaesthetised guinea-pigs, bronchoconstriction induced by vagal nerve stimulation was potentiated by low doses of the antimuscarinic bronchodilator drug, ipratropium (0.01-1.0 ?g/kg); the maximum effect was obtained with 1.0 ?g/kg which doubled the bronchoconstriction. When the dose was increased above 1.0 ?g/kg potentiation no longer occurred; instead the vagally induced bronchoconstriction was antagonized [1, 2].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[References]

[1]. Fryer, A.D. and J. Maclagan, Ipratropium bromide potentiates bronchoconstriction induced by vagal nerve stimulation in the guinea-pig. Eur J Pharmacol, 1987. 139(2): p. 187-91.

[2]. Harvey, K.L., A. Hussain, and H.L. Maddock, Ipratropium Bromide-Mediated Myocardial Injury in In Vitro Models of Myocardial Ischaemia/Reperfusion. Toxicol Sci, 2014.

[Related Small Molecules]

Chemical & Physical Properties

[ Melting Point ]:
230-232°C

[ Molecular Formula ]:
C₂₀H₃₀BrNO₃

[ Molecular Weight ]:
412.361

[ Exact Mass ]:
411.140900

[ PSA ]:
46.53000

[ Storage condition ]:
Store at RT

[ Stability ]:
Stable. Incompatible with strong oxidizing agents.

[ Water Solubility ]:
Freely soluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YM3700000

CHEMICAL NAME :: 1-alpha-H,5-alpha-H-Tropanium, 3-alpha-hydroxy-8-isopropyl-, bromide, (+-)-tropate

CAS REGISTRY NUMBER :: 22254-24-6

LAST UPDATED :: 199312

DATA ITEMS CITED :: 26

MOLECULAR FORMULA :: C20-H30-N-O3.Br

MOLECULAR WEIGHT :: 412.42

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Standard Draize test

ROUTE OF EXPOSURE :: Administration into the eye

SPECIES OBSERVED :: Rodent - rabbit

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 21,5692,1987 ** ACUTE TOXICITY DATA **

TYPE OF TEST :: TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :: Inhalation

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 1 ug/kg

TOXIC EFFECTS :: Gastrointestinal - other changes

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 292,380,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1663 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 113 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia Behavioral - tetany Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,176,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 635 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia Behavioral - tetany Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,176,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15700 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,489,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1001 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 72 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - coma Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 12290 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1300 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,985,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 1557 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - species unspecified

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage)

REFERENCE :: PMESAJ Postgraduate Medical Journal, Supplement. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1949- Volume(issue)/page/year: 51(Suppl 7),82,1975 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 33600 mg/kg/4W-C

TOXIC EFFECTS :: Behavioral - food intake (animal) Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 91 gm/kg/26W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Kidney, Ureter, Bladder - changes in bladder weight Endocrine - changes in adrenal weight

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 35 gm/kg/5W-I

TOXIC EFFECTS :: Brain and Coverings - changes in brain weight Cardiac - changes in heart weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,176,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 11200 mg/kg/4W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5500 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,971,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13500 mg/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,393,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 30 gm/kg

SEX/DURATION :: male 60 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,393,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 55 mg/kg

SEX/DURATION :: female 7-17 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 - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,971,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 550 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,971,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 65 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,393,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1120 mg/kg

SEX/DURATION :: male 28 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,417,1978 *** REVIEWS *** TOXICOLOGY REVIEW PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,489,1979

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R20/22

[ Safety Phrases ]:
S26

[ WGK Germany ]:
3

[ HS Code ]:
2933990090

Preparation

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%