pyridostigmine bromide

Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor.Target: AChEPyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and does not cross the blood–brain barrier, except possibly in stressful conditions. Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. It is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier which carbamylates about 30% of peripheral cholinesterase enzyme. The carbamylated enzyme eventually regenerates by natural hydrolysis and excess ACh levels revert to normal.Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis and to combat the effects of curariform drug toxicity. Pyridostigmine bromide has been FDA approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent Soman in order to increase survival. Used in particular during the first Gulf War, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome. Pyridostigmine sometimes is used to treat orthostatic hypotension. It may also be of benefit in chronic axonal polyneuropathy.

Signaling Pathways >> Neuronal Signaling >> AChE

Research Areas >> Neurological Disease

[1]. Gales BJ, et al. Pyridostigmine in the treatment of orthostatic intolerance. Ann Pharmacother. 2007 Feb;41(2):314-8. Epub 2007 Feb 6.

[2]. Kanjwal K, et al. Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. Pacing Clin Electrophysiol. 2011 Jun;34(6):750-5.

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MOLECULAR FORMULA :

C9-H13-N2-O2.Br

MOLECULAR WEIGHT :

261.15

WISWESSER LINE NOTATION :

T6KJ A1 COVN1&1 &E

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

7800 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations Sense Organs and Special Senses (Eye) - visual field changes Gastrointestinal - nausea or vomiting

REFERENCE :

IJMDAI Israel Journal of Medical Sciences. (POB 1435, Jerusalem 91013, Israel) V.1- 1965- Volume(issue)/page/year: 27,659,1991

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

9 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations

REFERENCE :

IJMDAI Israel Journal of Medical Sciences. (POB 1435, Jerusalem 91013, Israel) V.1- 1965- Volume(issue)/page/year: 27,659,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

37500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1042,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2699 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 4,S195,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 26,145,1983

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2790 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 7,507,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

16 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

GNRIDX Gendai no Rinsho. (Tokyo, Japan) V.1-10, 1967-76(?). Volume(issue)/page/year: 2,828,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,354,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1500 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

GNRIDX Gendai no Rinsho. (Tokyo, Japan) V.1-10, 1967-76(?). Volume(issue)/page/year: 2,828,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

MECHAN Medicinal Chemistry, A Series of Reviews. (New York, NY) V.1-6, 1951-63. Discontinued. Volume(issue)/page/year: 3,329,1956 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1350 mg/kg/15D-C

TOXIC EFFECTS :

Blood - other changes Musculoskeletal - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase

REFERENCE :

TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)- 1978- Volume(issue)/page/year: 18,387,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

140 mg/kg/14D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from small intestine Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase Related to Chronic Data - death

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,40,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

168 mg/kg/28D-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,40,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

540 mg/kg/90D-I

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,40,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Bird - chicken

DOSE/DURATION :

225 mg/kg/9W-I

TOXIC EFFECTS :

Blood - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase

REFERENCE :

JTEHD6 Journal of Toxicology and Environmental Health. (Hemisphere Pub., 1025 Vermont Ave., NW, Washington, DC 20005) V.1- 1975/76- Volume(issue)/page/year: 48,35,1996 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

630 mg/kg

SEX/DURATION :

female 14 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 69,291,1991

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

280 mg/kg

SEX/DURATION :

female 15-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 69,291,1991

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

300 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - physical

REFERENCE :

TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 69,291,1991 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 81490 No. of Facilities: 58 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 230 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 81490 No. of Facilities: 46 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 1619 (estimated) No. of Female Employees: 791 (estimated)