Physostigmine

Names

[ CAS No. ]:
57-47-6

[ Name ]:
Physostigmine

[Synonym ]:
Eserine Blue
Antilirium
(-)-Eserine
EINECS 200-332-8
Pyrrolo[2,3-b]indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS,8aR)-
Eserine
Physostigmine
(3aS-cis)-1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol Methylcarbamate (Ester)
Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis)-
Methanol, 1-[[(3aS,8aR)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-yl]oxy]-1-(methylimino)-, (E)-
MFCD00151090
(3aS,8aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate
Physostigmine (USP)
(3aS,8aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl hydrogen methylcarbonimidate
(3aS-cis)-1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo(2,3-b)indol-5-ol methylcarbamate (ester)
[(3aR,8bS)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-methylcarbamate
Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS,8aR)-
Pyrrolo[2,3-b]indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis)-

Biological Activity

[Description]:

Physostigmine (Eserine) is a reversible acetylcholinesterase (AChE) inhibitor. Physostigmine can crosses the blood-brain barrier and elevate acetylcholine levels in the brain. Physostigmine can reverse memory deficits in transgenic mice with Alzheimer's disease. Physostigmine is also an antidote for anticholinergic poisoning[1][2][3].

[Related Catalog]:

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

[In Vivo]

Physostigmine (Eserine) (0.03-0.3 mg/kg; s.c.; daily for 6 weeks) improves deficits in contextual and cued memory in Tg(+) mice[2]. Animal Model: Heterozygous transgenic mice (Tg(+) mice)[2] Dosage: 0.03, 0.1, and 0.3 mg/kg Administration: S.c.; daily for 6 weeks Result: Tended to normalize the contextual memory deficit in Tg(+) animals so that they became more similar to Tg(-) animals.

[References]

[1]. Haase U, et al. Pharmakotherapie--physostigmin post OP [Pharmacotherapy--physostigmine administered post-operatively]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2007;42(3):188‐189.

[2]. Dong H, et al, Bertchume A, Vallera D, Csernansky JG. Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer's disease. Psychopharmacology (Berl). 2005;181(1):145‐152.

[3]. Frascogna N. Physostigmine: is there a role for this antidote in pediatric poisonings?. Curr Opin Pediatr. 2007;19(2):201‐205.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
422.3±55.0 °C at 760 mmHg

[ Melting Point ]:
102-104 °C(lit.)

[ Molecular Formula ]:
C₁₅H₂₁N₃O₂

[ Molecular Weight ]:
275.346

[ Flash Point ]:
209.2±31.5 °C

[ Exact Mass ]:
275.163391

[ PSA ]:
44.81000

[ LogP ]:
1.89

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.616

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TJ2100000

CHEMICAL NAME :: Physostigmine

CAS REGISTRY NUMBER :: 57-47-6

LAST UPDATED :: 199710

DATA ITEMS CITED :: 27

MOLECULAR FORMULA :: C15-H21-N3-O2

MOLECULAR WEIGHT :: 275.39

WISWESSER LINE NOTATION :: T B556 EN GNTT&J B1 E1 G1 KOVM1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Behavioral - coma Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - nausea or vomiting

REFERENCE :: 34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969 Volume(issue)/page/year: -,475,1969

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 40 ug/kg/5D-I

TOXIC EFFECTS :: Vascular - BP elevation not characterized in autonomic section

REFERENCE :: AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,910,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 3920 ug/kg/2W-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity

REFERENCE :: NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,345,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 12 mg/kg/60D-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity

REFERENCE :: NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,345,1987

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 882 ug/kg

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

REFERENCE :: 85DCAI "Poisoning; Toxicology, Symptoms, Treatments," 2nd ed., Arena, J.M., Springfield, IL, C.C. Thomas, 1970 Volume(issue)/page/year: 2,73,1970

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2 mg/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: 22,1926,1972

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3 mg/kg

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

REFERENCE :: 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 644 ug/kg

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :: FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 43,717,1980

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 740 ug/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 123,121,1958

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 400 ug/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 58,337,1936

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 330 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: 33,577,1990

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

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 600 ug/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5306825

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1138 ug/kg

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - ulceration or bleeding from large intestine

REFERENCE :: FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 5,184,1946

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 660 ug/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 88,39,1946

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 11200 ug/kg

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

REFERENCE :: DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 3,319,1980

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 2470 ug/kg

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

REFERENCE :: ABMHAM Archives Belges de Medecine Sociale, Hygiene, Medecine du Trevail et Medecine Legale. (Quartier Esplanade no.6, 1010 Brussels, Belgium) V.4- 1946- Volume(issue)/page/year: (Suppl),226,1984

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 3 mg/kg

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

REFERENCE :: 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 500 ug/kg

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

REFERENCE :: 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 2200 ug/kg

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

REFERENCE :: DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 3,319,1980

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Bird - pigeon

DOSE/DURATION :: 450 ug/kg

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

REFERENCE :: HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1289,1935

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

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Mammal - species unspecified

DOSE/DURATION :: 600 ug/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5409948 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 333 ug/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

REFERENCE :: ANENAG Annales d'Endocrinologie. (Masson Editeur, 120 Blvd. Saint-Germain, F-25280 Paris Cedex 06, France) V.1- 1939- Volume(issue)/page/year: 24(Suppl 3),1,1963

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 ug/kg

SEX/DURATION :: female 13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - biochemical and metabolic Reproductive - Effects on Newborn - behavioral

REFERENCE :: FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 31,596,1972 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4159 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 103 (estimated) No. of Female Employees: 52 (estimated)

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300 + H330

[ Precautionary Statements ]:
P260-P284-P301 + P310 + P330-P304 + P340 + P310-P403 + P233

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T+

[ Risk Phrases ]:
26/28

[ Safety Phrases ]:
S23-S45-S25

[ RIDADR ]:
UN 1544 6.1/PG 1

[ WGK Germany ]:
3

[ RTECS ]:
TJ2100000

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1(a)

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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Related Compounds

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