Rilmazafone Hydrochloride

Rilmazafone is a new hypnotic with anxiolytic properties. The major advantages of rilmazafone are claimed to be a significant reduction of motor ataxia and the lack of habituation or hang-over associated with other hypnotics.

When the animals are pretreated with high doses of Rilmazafone hydrochloride (450191-S; 200 or 600 mg/kg for 5 or 3 days, respectively) to induce hepatic drug-metabolizing enzymes, plasma concentrations of the metabolites after oral administration of a dose of 200 mg/kg of Rilmazafone decrease markedly depending on the induced enzyme activity. Pretreatment of rats with phenobarbital also causes decreased plasma levels of metabolites, which are almost the same as those in Rilmazafone-pretreatment. On the other hand, administration of beta-naphthoflavone to rats leads to higher plasma levels of metabolites, and slower elimination compared with those in the control and Rilmazafone or Phenobarbital pretreated rats. Rilmazafone is demonstrated to stimulate the hepatic drug-metabolizing enzymes in rats, mice and dogs, which is accompanied by a marked reduction in the pharmacological activity of pentobarbital in rats. The induction of hepatic enzyme activities by Rilmazafone is detected only when the plasma concentrations of its metabolites are very high.

Mice
Adult male rats of the Jcl Sprague-Dawley strain, 7-8 weeks old, are used for the experiments. The animals are kept in an airconditioned room (25±1°C, 50-60% humidity) lighted 12 hr a day (8:00-20:00) and maintain on com mercial rat chow and
water ad libitum. Rilmazafone is dissolved in 5% (w/v) arabic gum at 20 or 60 mg/mL, and the resulting solution is
administered orally to rats at 1.0 mL/100 g body weight for 3-5 days. Typical inducers, phenobarbital (in physiological
saline) and beta-naphthoflavone (in sesame oil), are administered intraperitoneally at a dose of 40 mg/kg, once daily for 3
days. The animals are fasted for 24 hr after the last adminis tration of Rilmazafone or inducers, and then the test solution of
Rilmazafone (20 mg/mL of 5% arabic gum) is given orally to rats at a dose of 200 mg/kg. Heparinized blood samples are
obtained from the abdominal aorta under ether anesthesia and centrifuged immediately to obtain plasma samples using an
Eppendorf centrifuge Type 5414S.

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