Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal Δ9-tetrahydrocannabinol
Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal Δ9-tetrahydrocannabinol
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DOI：
10.1016/j.ejphar.2005.09.039
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发表时间：
2005-11-21
影响因子：
5
通讯作者：
Smith, FL
中科院分区：
文献类型：
--
作者：
Cichewicz, DL;Welch, SP;Smith, FL
先前的研究已经证明，Delta（9）-四氢大麻酚（THC）增强了通过各种不同给药途径施用的许多阿片类药物的抗伤害感受效力。我们假设THC通过经皮给药途径增强芬太尼或丁丙诺啡镇痛。当使用针刺试验在无毛豚鼠模型中胃肠外给予两种药物时，THC首次被证明可增强阿片类抗伤害感受。低剂量的THC（50 mg/kg，i. p.）不产生抗伤害感受。然而，THC增强了s.c.芬太尼增加6.7倍，s.c.丁丙诺啡以非平行的方式。对于透皮研究，通过移液管将THC、芬太尼或丁丙诺啡施加到前腹和后腹之间的背部皮肤上，并用单独的TegedermTM贴剂覆盖。THC（400 mg/kg）无镇痛作用。然而，THC在2小时时将芬太尼的效力提高了3.7倍，在4小时时提高了5.8倍。当与THC共同施用时，丁丙诺啡的效力在2小时增加8.2倍，在4小时增加7.2倍。这些结果表明，THC对阿片类药物透皮吸收的增强作用可能会导致设计所有有效的组合镇痛贴剂。(c)2005 Elsevier B. V.保留所有权利。
Previous studies have demonstrated that Delta(9)-tetrahydrocannabinol (THC) enhances the antinociceptive potency of many opioids administered by a variety of different routes of administration. We hypothesized that THC would enhance fentanyl or buprenorphine analgesia via the transdermal route of administration. THC was first demonstrated to enhance opioid antinociception when both drugs were administered parenterally in a hairless guinea pig model using the pin prick test. A low dose of THC (50 mg/kg, i.p.) produced no antinociception. However, THC enhanced the potency of s.c. fentanyl by 6.7-fold, and s.c. buprenorphine in a non-parallel fashion. For the transdermal studies, THC, fentanyl or buprenorphine was applied by pipette to the skin of the dorsum between the fore- and hind-flanks and covered with individual Tegederm (TM) patches. THC (400 mg/kg) produced no antinociception. However, THC enhanced fentanyl's potency by 3.7-fold at 2-h, and 5.8-fold at 4-h. Buprenophine's potency was increased 8.2-fold at 2-h and 7.2-fold at 4-h when co-administered with THC. These results indicate that the enhancement of transdermal opioids by THC could lead to the design of ail effective combination analgesic patch. (c) 2005 Elsevier B.V. All rights reserved.