Wong C H, Zbuzek V K, Wu W H
Department of Anesthesiology, Chang Gung Memorial Hospital, Taipei, Taiwan.
Life Sci. 1996;59(18):PL277-81. doi: 10.1016/0024-3205(96)00489-4.
We confirmed that repeated injection of nifedipine evokes an acute tolerance in rats. Nociceptive response was assessed by the tail-flick test. Rats, randomly divided into 3 groups, were injected once a week for 1 month with nifedipine intraperitoneally at the doses of: (A) 2 mg/kg; (B) 10 mg/kg; and (C) 10 mg/kg at the first injection and followed by dimethyl sulfoxide in the subsequent injections. After one month, group A and C were injected with 10 mg/kg and group B with 30 mg/kg nifedipine. In group A, 2 mg/kg of nifedipine did not change the TF latency but its repeated injections prevented the antinociceptive effect of 10 mg/kg nifedipine. In group B, only the first dose of 10 mg/kg and the last dose of 30 mg/kg produced a significant antinociception. In group C, the first but not the last dose of 10 mg/kg nifedipine, produced a significant antinociception. Our data suggest that a single dose of 10 mg/kg nifedipine or repeated doses of 2 mg/kg produced a tolerance-like phenomenon in nifedipine-induced antinociception.
我们证实，重复注射硝苯地平会在大鼠中引发急性耐受性。通过甩尾试验评估伤害性反应。将大鼠随机分为3组，每周腹腔注射一次硝苯地平，持续1个月，剂量分别为：(A)2 mg/kg；(B)10 mg/kg；(C)首次注射10 mg/kg，随后注射二甲基亚砜。1个月后，A组和C组注射10 mg/kg，B组注射30 mg/kg硝苯地平。在A组中，2 mg/kg的硝苯地平未改变甩尾潜伏期，但其重复注射可防止10 mg/kg硝苯地平的抗伤害性作用。在B组中，仅首次10 mg/kg剂量和最后30 mg/kg剂量产生了显著的抗伤害作用。在C组中，首次10 mg/kg硝苯地平剂量产生了显著的抗伤害作用，但最后一次剂量未产生。我们的数据表明，单次10 mg/kg硝苯地平剂量或重复2 mg/kg剂量会在硝苯地平诱导的抗伤害作用中产生类似耐受性的现象。
