Zoxazolamine

Zoxazolamine is widely used for a pharmacologic test that serves as a convenient indicator of changes in cytochrome P-450 activity in rodents.

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Research Areas >> Neurological Disease

Zoxazolamine is widely used for a pharmacologic test that serves as a convenient indicator of changes in cytochrome P-450 activity in rodents. The time-averaged serum clearance determined from tested concentrations data is 7.22±1.01 mL/min/kg for Zoxazolamine. Infusion of Zoxazolamine to righting reflex (LRR) at three different rates shows increasing Zoxazolamine concentration in serum and brain at the onset of the effect with increasing infusion rates. When the Zoxazolamine infusion is continued for 5 min beyond the onset of LRR, the concentrations of Zoxazolamine in the cerebrospinal fluid (CSF) at the offset of LRR are essentially identical to the onset concentrations[1].

Inbred male Lewis rats are used in this study. The animals are allowed 7 to 12 days to adjust to the local animal facilities and to recover possible stress incurred during transport. To compare drug concentrations in serum at the onset and offset of loss of the righting reflex, Zoxazolamine is infused into the femoral vein at a rate of 0.51 mg/min for 5 min beyond the onset of loss of the righting reflex. The infusion solution consists of 10 mg Zoxazolamine in 1 mL normal saline. Then, blood samples from the jugular vein are obtained from four rates at the onset and offset of loss of the righting reflex, using a procedure that yields mainstream blood[1].

[1]. Yasuhara M, et al. Pharmacodynamics of zoxazolamine and chlorzoxazone in rats. Pharm Res. 1988 Jul;5(7):401-7.

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MOLECULAR FORMULA :

C7-H5-Cl-N2-O

MOLECULAR WEIGHT :

168.59

WISWESSER LINE NOTATION :

T56 BN DOJ CZ HG

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1607 mg/kg/34W-I

TOXIC EFFECTS :

Liver - jaundice, other or unclassified

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 176,874,1961

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

14 mg/kg/D

TOXIC EFFECTS :

Behavioral - stiffness

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 160,745,1956

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

782 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic)

REFERENCE :

FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 16,319,1957

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

102 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - muscle weakness Behavioral - ataxia

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: 129,75,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

540 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - ataxia

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: 128,112,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: AD277-689

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

376 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

29QHAQ "Principles of Medicinal Chemistry," Foye, W.O., et al., eds., Philadelphia, Lea & Febiger, 1974 Volume(issue)/page/year: -,246,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

117 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic)

REFERENCE :

FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 16,319,1957

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

670 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - muscle weakness Behavioral - ataxia

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: 129,75,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

268 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - muscle weakness Behavioral - ataxia

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: 129,75,1960 *** REVIEWS *** TOXICOLOGY REVIEW AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 38,409,1965