QUINIDINE SULFATE (2:1) (salt)

Quinidine Monosulfate is an antiarrhythmic agent. Quinidine Monosulfate is a potent, orally active, selective cytochrome P450db inhibitor. Quinidine Monosulfate is also a K+ channel blocker with an IC50 of 19.9 μM. Quinidine Monosulfate can be used for malaria research[1][2][3].

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Research Areas >> Infection

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Quinidine is an anti-arrythmic drug which affects ionic currents in heart muscle and which has also been shown to be a potent blocker of several classes of K+ channel in a variety of cell types[1]. Bath application of quinidine causes a dose-dependent reduction of the peak amplitude of Ik. The Kd for blockade of Ik at 0 mV is estimated to be 41 μM[1]. Quinidine elicits a dose-dependent increase of the rate of the decay of Ik and this effect is enhanced by membrane depolarization. Quinidine also causes a 5 mV hyperpolarizing shift of the steady-state inactivation curve and increases the half-time for recovery from inactivation. Quinidine does not affect the onset of inactivation measured at -30 mV[1].

Quinidine sulfate is rapidly absorbed, with peak plasma concentrations 60-90 min after an oral dose. Other salts (gluconate, polygalacturonate) are more slowly absorbed, with lower peak concentrations[2]. Quinidine is approximately 70-90 % bound to plasma proteins. It undergoes hepatic oxidative metabolism to form an N-oxide, a 3-hydroxy form, an O-demethyl form and 2'-quinidinone. Over one-half of patients starting quinidine stop within the first year of therapy because of side effects. These include, commonly, diarrhea, nausea, and vomiting which are not necessarily related to high plasma concentrations[2]. Quinidine inhibits metabolism of amphetamine in rats. Quinidine pretreatment results in a significant decrease in the excretion of p-hydroxyamphetamine at 24 and 48 h to 7.2 and 24.1% of the vehicle-control levels, respectively, accompanied by a significant increase in amphetamine excretion between 24 and 48 h to 542% of the control[3].

[1]. Kehl SJ, et al. Quinidine-induced inhibition of the fast transient outward K+ current in rat melanotrophs. Br J Pharmacol. 1991 Jul;103(3):1807-13.

[2]. Roden DM, et al. Class I antiarrhythmic agents: quinidine, procainamide and N-acetylprocainamide, disopyramide.

[3]. Moody DE, et al. Quinidine inhibits in vivo metabolism of amphetamine in rats: impact upon correlation between GC/MS and immunoassay findings in rat urine. J Anal Toxicol. 1990 Sep-Oct;14(5):311-7.

MOLECULAR WEIGHT :

747.00

WISWESSER LINE NOTATION :

T66 BNJ HO1 EYQ- DT66 A B CNTJ G1U1 &WSQQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

240 mg/kg/2W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - conjunctive irritation Endocrine - tumors Musculoskeletal - joints

REFERENCE :

JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 20,367,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

272 mg/kg/17D-I

TOXIC EFFECTS :

Vascular - other changes

REFERENCE :

AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 145,2051,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

386 mg/kg/30D-I

TOXIC EFFECTS :

Blood - changes in cell count (unspecified) Nutritional and Gross Metabolic - body temperature increase

REFERENCE :

AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 77,345,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

9600 mg/kg/8W

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - tremor Lungs, Thorax, or Respiration - other changes

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 238,884,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

409 gm/kg/14Y

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 237,2093,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

88 mg/kg/10D-I

TOXIC EFFECTS :

Liver - hepatitis (hepatocellular necrosis), diffuse Nutritional and Gross Metabolic - body temperature increase Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :

GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1943- Volume(issue)/page/year: 70,1136,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

32 mg/kg/2D

TOXIC EFFECTS :

Skin and Appendages - dermatitis, irritative (after systemic exposure)

REFERENCE :

DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969- Volume(issue)/page/year: 16,615,1982

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Multiple routes

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

30 mg/kg/2D-I

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 16,571,1942

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

456 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: 18,1127,1968

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

140 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: 1,156,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

610 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: 18,1127,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

55 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 44,187,1992

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

505 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

135 mg/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: 124,53,1958

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

54 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 105,221,1956

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

19 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :

DECRDP Drugs under Experimental and Clinical Research. (Bioscience Ediprint, Blvd. James-Fazy 13, 1201 Geneva 1, Switzerland) V.1- 1977- Volume(issue)/page/year: 10,197,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

16 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 32,833,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

30 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 32,833,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

362 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

117 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80504 No. of Facilities: 101 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 3397 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80504 No. of Facilities: 178 (estimated) No. of Industries: 3 No. of Occupations: 6 No. of Employees: 2948 (estimated) No. of Female Employees: 1491 (estimated)