Effect of fentanyl on lidocaine-induced convulsions in mice.
This study was undertaken to examine the effect of fentanyl on lidocaine-induced convulsions in mice. Seventy-five male mice were used and divided into five groups, 15 in each. Convulsions were obtained by lidocaine injection subcutaneously (150 mg/kg), in a dose volume of 0.1 ml/10 g body weight over the upper back. The five groups were: (a) control group: pretreated with normal saline; (b) F50 group: pretreated with fentanyl 50 microg/kg; (c) F100 group: pretreated with fentanyl 100 microg/kg; (d) F200 group: pretreated with fentanyl 200 microg/kg, and (e) F100+N group: pretreated with fentanyl 100 mug/kg plus naloxone 1 mg/kg. The pretreatments were given intraperitoneally (i.p.) 5 min prior to lidocaine injection. After lidocaine injection, the latency to the onset of generalized convulsions was observed for 12 min and recorded. The severity of convulsions was assessed and scored as 1 = mild, 2 = moderate, and 3 = severe. The recovery or death of the mice were also recorded. Student's t, Mann-Whitney U, and Fisher's exact tests were used to analyze the data. Compared with the control group (431.7 +/- 37.3 s), the latencies of onset of convulsions in the fentanyl groups were dose-dependently decreased (F50: 331.0 +/- 37.1 s; F100: 240.3 +/- 28.6 s, p < 0.001; F200: 188.7 +/- 19.4 s, p < 0.001), and the decreased latency was reversed by naloxone (F100+N: 412.9 +/- 34.1 s). Compared with the control group (1.13 +/- 0.19), the severities of convulsions in the fentanyl groups were also increased in a dose-dependent manner (F50: 1.47 +/- 0.19; F100: 1.93 +/- 0.21, p < 0.05; F200: 2.46 +/- 0.17, p < 0.001). Similarly, the increased severity was reversed by naloxone (F100+N: 1.33 +/- 0.16). There was no death in the control and naloxone-treated groups. The incidences of death were 2/15 in F50 group, 5/15 in F100 group, and 7/15 in the F200 group (p < 0.05). The results of this study demonstrated that fentanyl potentiates the lidocaine-induced convulsions in a dose-dependent manner in mice, and this effect may be mediated by an opioid mechanism.
Cherng
Chen-Hwan
CH
Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. cherng1018@yahoo.com.tw
Wong
Chih-Shung
CS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008012:Lidocaine; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D011229:Preanesthetic Medication; D012640:Seizures / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D008012:Lidocaine; D005283:Fentanyl