Bannon A W, Gunther K L, Decker M W
Pharmaceutical Products Division, Abbott Laboratories, IL 60064-3500, USA.
Pharmacol Biochem Behav. 1995 Aug;51(4):693-8. doi: 10.1016/0091-3057(94)00439-p.
The experiments in the present study were designed to determine if the activity, temperature, and analgesic effects of (+/-)-epibatidine treatment could be dissociated. Initially (i.e., 15 min) (+/-)-epibatidine treatment (0.1 mumol/kg = 28 micrograms/kg, IP) impaired rotorod performance, decreased activity, decreased temperature, and increased jump latency (e.g., analgesic effect). For the remaining time points measured (i.e., 30, 60, and 120 min), activity and temperature remained significantly reduced. In contrast, by 120 min (+/-)-epibatidine's effects on rotorod performance and analgesia (jump latency) were not observed. When administered after (+/-)-epibatidine (0.05 mumol/kg, IP), mecamylamine treatment (5 mumol/kg = 1 mg/kg, IP) produced a potentiation of analgesia. This potentiation effect was not observed on activity and temperature measures. The effect of (+/-)-epibatidine treatment (0.1 mumol/kg, IP) was also determined in mice with central nicotinic receptor blockade induced by treatment with chlorisondamine (23 mumol/kg = 10 mg/kg, IP). An (+/-)-epibatidine-induced reduction in activity was not attenuated in chlorisondamine-treated mice and only a minimal effect was observed on (+/-)-epibatidine-induced hypothermia in chlorisondamine-treated mice. In contrast, in chlorisondamine-treated mice (+/-)-epibatidine's analgesic effect was attenuated. Taken together, these data suggest that various centrally mediated effects of (+/-)-epibatidine can be dissociated.
本研究中的实验旨在确定（±）-埃博霉素治疗的活性、温度和镇痛作用是否可以分离。最初（即15分钟），（±）-埃博霉素治疗（0.1 μmol/kg = 28 μg/kg，腹腔注射）损害了转棒性能，降低了活性，降低了温度，并增加了跳跃潜伏期（例如，镇痛作用）。在其余测量的时间点（即30、60和120分钟），活性和温度仍显著降低。相比之下，到120分钟时，未观察到（±）-埃博霉素对转棒性能和镇痛（跳跃潜伏期）的影响。在（±）-埃博霉素（0.05 μmol/kg，腹腔注射）给药后，美加明治疗（5 μmol/kg = 1 mg/kg，腹腔注射）产生了镇痛增强作用。这种增强作用在活性和温度测量中未观察到。还在经氯异吲哚胺（23 μmol/kg = 10 mg/kg，腹腔注射）治疗诱导中枢烟碱受体阻断的小鼠中测定了（±）-埃博霉素治疗（0.1 μmol/kg，腹腔注射）的效果。在氯异吲哚胺治疗的小鼠中，（±）-埃博霉素引起的活性降低未减弱，并且在氯异吲哚胺治疗的小鼠中，仅观察到对（±）-埃博霉素诱导的体温过低的最小影响。相比之下，在氯异吲哚胺治疗的小鼠中，（±）-埃博霉素的镇痛作用减弱。综上所述，这些数据表明（±）-埃博霉素的各种中枢介导作用可以分离。
