Effects of furazolidone on duration of righting reflex loss induced with hexobarbital and zoxazolamine in the rat.
Effects of furazolidone (FZ) on the sleeping time induced with hexobarbital (HEX) and paralysis time induced by zoxazolamine (ZOX) were investigated by measuring the length of time required to recover from righting reflex loss in rats after oral administration of FZ at doses of 50, 100, 200 and 400 mg/kg/day for 4 successive days. Administration of 50 mg/kg to rats of both sexes induced no effect on the HEX sleeping time, but of 100 mg/kg FZ or more induced prolongation of sleeping time dose-dependently. In female rats, HEX sleeping time of the control group was twice that of the male rats, but HEX sleeping time after receiving FZ above 200 mg/kg was approximately the same as in the male rats. ZOX paralysis time exhibited no sex differences in the control rats, and it was significantly prolonged by FZ at a dose of 100 mg/kg or more. No significant differences in blood levels of HEX and ZOX at the time of recovery were found between the control and FZ treated rats, suggesting that FZ produced prolongation of the drug effects was due to the maintenance of the blood levels rather than the change in the sensitivities of rats at the receptor sites. Body weight gains were inhibited in the rats treated with FZ at doses over 100 mg/kg. Cytochrome P-450 content in hepatic microsomes in the rats which received 100 mg/kg FZ were slightly increased. It is suggested that successive oral administration of FZ to rats at high doses impaired drug clearance and this resulted in the prolongation of HEX sleeping and ZOX paralysis times.
Sasaki
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National Veterinary Assay Laboratory, Tokyo, Japan.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005664:Furazolidone / Q000008:administration & dosage / Q000494:pharmacology*; D006591:Hexobarbital / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D015049:Zoxazolamine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D005664:Furazolidone; D003577:Cytochrome P-450 Enzyme System; D015049:Zoxazolamine; D006591:Hexobarbital