Phensuximide

Phensuximide is an orally active succinimide antiepileptic and anticonvulsant agent. Phensuximide inhibits cyclic AMP and cyclic GMP accumulation in depolarized brain tissue. Phensuximide can be used for the study of seizure and petit mal[1][3].

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

IC50: cyclic AMP and cyclic GMP accumulation[2]

Phensuximide produce depolarization-induced accumulation of cyclic GMP or cyclic AMP levels with ID50 values of 8.00 mM or 6.20 mM in incubated slices of mouse cerebral cortex[2]. Phensuximide (0.5-2.0 mM) has the ability to competitively inhibit mephenytoin 4-hydroxylase activity in human liver microsomes, the Ki and Km values are 559 μM and 235 μM, respectively[4].

Phensuximide (intraperitoneal injection; 1.25 mmol/kg; single dose) induces mild changes in renal function, including: trace hematuria, increased proteinuria and decreased paminohippurate uptake in Sprague-Dawley rats[1]. Phensuximide (intraperitoneal injection; 0.3 or 0.6 mmol/kg; 5-7 days) results in transient hematuria and proteinuria, but no change in the other renal function parameters studied. It is concluded that phensuximide produces mild, transient renal effects in Fischer 344 rats, and that the Fischer 344 rat is a suitable model for studying phensuximide-induced toxicity to the urinary tract[1]. Animal Model: Fischer 344 rats[1] Dosage: 0.3 or 0.6 mmol/kg Administration: Intraperitoneal injection; 5-7 days Result: Induced urotoxicity following daily administration for 5-7 days in Fischer 344 rats.

[1]. G O Rankin, et al. Urinary Tract Effects of Phensuximide in the Sprague-Dawley and Fischer 344 Rat. J Appl Toxicol. . 1986 Oct;6(5):349-56.

[2]. J A Ferrendelli, et al. Inhibitory Effects of Anticonvulsant Drugs on Cyclic Nucleotide Accumulation in Brain. Ann Neurol. 1979 Jun;5(6):533-8.

[3]. J G MILLICHAP, et al. Milontin: A New Drug in the Treatment of Petit Mal.Lancet. 1952 Nov 8;2(6741):907-10.

[4]. S D Hall,et al. Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes. The JOURNAL OP PHARMAcOLOGY AND EXPERIMENTAL THERAPEUTICS

DATA ITEMS CITED :

7

MOLECULAR FORMULA :

C11-H11-N-O2

MOLECULAR WEIGHT :

189.23

WISWESSER LINE NOTATION :

T5VNVTJ B1 DR

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

700 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

485 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

795 mg/kg/7D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - proteinuria Kidney, Ureter, Bladder - hematuria Kidney, Ureter, Bladder - inflammation, necrosis, or scarring of bladder

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

666 mg/kg

SEX/DURATION :

female 8-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1533 mg/kg

SEX/DURATION :

female 8-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Human Leukocyte

DOSE/DURATION :

100 ug/L

REFERENCE :

AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 116,867,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4457 No. of Facilities: 46 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 279 (estimated) No. of Female Employees: 46 (estimated)