Combined effect of flunitrazepam on activities of anesthetics and analgesics in mice and rats

Abstract

Flunitrazepam in a dose range of 0.01 to 1 mg/kg i.v. produced dose dependent sedation and muscle relaxation, while even 1 mg/kg of flunitrazepam had no anesthetic effect (loss of righting reflex). Flunitrazepam in a dose over 0.01 mg/kg prolonged anesthesia induced by pentobarbital, thiopental and ketamine in mice and rats and combinations of non-effective doses of these anesthetics with flunitrazepam induced anesthesia in mice. Furthermore, flunitrazepam enhanced gaseous anesthesia in mice and rats. Flunitrazepam alone was slightly effective in prevention of acetic acid writhing in mice and the drug enhanced the anti-writhing effects of morphine, pentazocine and thalamonal. Flunitrazepam alone had little analgesic effect on the hot plate test in mice, while it did enhance the effect of morphine. The analgesic effects of morphine and pentazocine on the tail pinch test in rats were potentiated with 0.1 and 1 mg/kg of flunitrazepam. Flunitrazepam had no effect on bradykinin-induced nociceptive response in rats, while 1 mg/kg of the drug enhanced morphine analgesia in this test. Combined effect of flunitrazepam on activities of anesthetics and analgesics may contribute to the clinical effect of this drug in cases of preanesthetic medication.