Abram S E, O'Connor T C
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 1995 Oct;83(4):844-9. doi: 10.1097/00000542-199510000-00025.
Intrathecal carbachol produces consistent analgesia in animals without appreciable adverse effects. Little is known about the ability of this drug to provide analgesia as stimulus intensity is increased. Likewise, there are few data regarding interactions between carbachol and other intrathecal analgesics.
Using two different noxious radiant heat intensities, one applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms intrathecal carbachol on paw withdrawal latencies were measured. Similar testing was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8, 1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were administered, responses to the low intensity stimulus were recorded, and the ED50 of each combination was established and isobolographic analysis of the drug interactions was carried out.
The 30-micrograms dose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED50 (95% confidence interval) of intrathecal carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64 micrograms (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED50 values for intrathecal morphine and clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive effects. The ED50 for the carbachol-morphine combination was 12% of the expected additive value and the ED50 for the carbachol-clonidine combination was 30% of the expected additive value.
Intrathecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing analgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine.
鞘内注射卡巴胆碱可在动物身上产生持续的镇痛作用，且无明显不良反应。关于该药物在刺激强度增加时提供镇痛的能力知之甚少。同样，关于卡巴胆碱与其他鞘内注射镇痛药之间相互作用的数据也很少。
使用两种不同强度的有害辐射热，分别施加于每只后肢，测量鞘内注射1、3、10和30微克卡巴胆碱对爪部退缩潜伏期的镇痛效果。对鞘内注射吗啡和可乐定进行类似测试。给予卡巴胆碱-吗啡和卡巴胆碱-可乐定药物组合的ED50分数（1/2、1/4、1/8、1/16），记录对低强度刺激的反应，确定每种组合的ED50并进行药物相互作用的等效应线分析。
30微克剂量的卡巴胆碱与短暂的躁动、流涎和后肢无力有关。未观察到其他不良反应。鞘内注射卡巴胆碱的ED50（95%置信区间）在低强度刺激时为2.34微克（1.34 - 4.04），在高强度刺激时为12.64微克（4.18 - 38.25）。鞘内注射吗啡和可乐定的高强度与低强度ED50值之间无显著差异。卡巴胆碱-吗啡和卡巴胆碱-可乐定组合的镇痛效果明显大于计算出的相加效应。卡巴胆碱-吗啡组合的ED50为预期相加值的12%，卡巴胆碱-可乐定组合的ED50为预期相加值的30%。
鞘内注射卡巴胆碱可为大鼠后爪的有害热刺激提供镇痛作用。当刺激强度增加时，其提供镇痛的效果相对不如鞘内注射吗啡或可乐定。鞘内注射卡巴胆碱与鞘内注射吗啡或可乐定联合使用时具有协同作用。
