Suzuki T, Narita M, Misawa M, Nagase H
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Life Sci. 1991;48(19):1827-35. doi: 10.1016/0024-3205(91)90238-7.
Pentazocine (PZ) is well known to act as an opioid mixed agonist-antagonist analgesic. In the present study, we selected the mouse warm plate test condition of 51 +/- 0.5 degrees C instead of 55 +/- 0.5 degrees C to determine the analgesic action of PZ. As a result, i.c.v. PZ produced a biphasic antinociceptive response, while U-50,488H (U-50) and morphine (MRP) showed a monophasic response. Pretreatment with i.c.v. beta-FNA (mu antagonist) antagonized the initial response, whereas the delayed one was antagonized by pretreatment with nor-BNI (kappa antagonist). In addition, pretreatment with NTI (delta antagonist) significantly attenuated the initial response but not the delayed one. These results suggest that the initial and delayed responses may be mediated mainly by mu/delta and kappa receptors, respectively. With regards to the interaction between MRP and PZ, a low dose of PZ antagonized the analgesic action of MRP, while a high dose PZ plus MRP showed the additive effect. Furthermore, tolerance developed almost equally to both initial and delayed responses, indicating that tolerance to the kappa component of PZ may be developed as well as the mu component of action of PZ.
喷他佐辛（PZ）作为一种阿片类混合激动 - 拮抗剂镇痛药而广为人知。在本研究中，我们选择51±0.5℃而非55±0.5℃的小鼠热板试验条件来测定PZ的镇痛作用。结果显示，脑室内注射PZ产生双相抗伤害感受反应，而U - 50,488H（U - 50）和吗啡（MRP）表现出单相反应。脑室内注射β - FNA（μ拮抗剂）预处理可拮抗初始反应，而延迟反应可被去甲 - BNI（κ拮抗剂）预处理所拮抗。此外，NTI（δ拮抗剂）预处理显著减弱初始反应，但不影响延迟反应。这些结果表明，初始反应和延迟反应可能分别主要由μ/δ受体和κ受体介导。关于MRP与PZ之间的相互作用，低剂量PZ拮抗MRP的镇痛作用，而高剂量PZ加MRP则表现出相加效应。此外，对初始反应和延迟反应的耐受性发展几乎相同，这表明对PZ的κ作用成分以及μ作用成分都可能产生耐受性。
