Centhaquin antinociception in mice is mediated by ¦Á_2A- and ¦Á_2B- but not ¦Á_2C-adrenoceptors

详细信息    查看全文

• 作者：Shaifali Bhalla ; Izna Ali ; Shridhar V. Andurkar ; Anil Gulati
• 关键词：Centhaquin citrate ; BRL-44408 ; Imiloxan ; JP-1302 ; Antinociception ; ¦Á2A- ; ¦Á2B- ; and ¦Á2C-adrenoceptors
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：5 September, 2013
• 年：2013
• 卷：715
• 期：1-3
• 页码：328-336
• 全文大小：1848 K

文摘

The use of clonidine as a primary and adjuvant analgesic is well-documented. It is known that imidazoline and ¦Á₂-adrenoceptors are involved in clonidine antinociception. Clonidine also produces antihypertensive actions mediated through the central nervous system. We have reported that centhaquin, a centrally-acting anti-hypertensive drug produces its hypotensive effect through a mechanism of action similar to clonidine. Centhaquin has also been shown to possess significant antinociceptive activity. Centhaquin antinociception is partially blocked by yohimbine, idazoxan, and naloxone; however, the involvement of specific adrenoceptor subtypes (¦Á_2A, ¦Á_2B, or ¦Á_2C) in centhaquin antinociception is unknown. The present study was conducted to determine antinociceptive properties of centhaquin citrate, a water soluble salt of centhaquin, and involvement of ¦Á_2A-, ¦Á_2B-, or ¦Á_2C-adrenoceptors in centhaquin citrate antinociception in mice. BRL-44408 (¦Á_2A-adrenoceptor antagonist), imiloxan (¦Á_2B-adrenoceptor antagonist) and JP-1302 (¦Á_2C-adrenoceptor antagonist) were used to determine the involvement of ¦Á_2A-, ¦Á_2B-, or ¦Á_2C-adrenoceptors, respectively. Antinociceptive (tail-flick and hot-plate) latencies were determined in male Swiss-Webster mice treated with centhaquin citrate alone and in combination with BRL-44408, imiloxan, or JP-1302. Centhaquin citrate produced significant antinociception in mice (P<0.05) which was unaffected by JP-1302 (P>0.05) but blocked by BRL-44408 (tail-flick test: 49.75 % decrease, P<0.05; hot-plate test: 49.12 % decrease, P<0.05) and imiloxan (tail-flick test: 46.98 % decrease, P<0.05; hot-plate test: 46.42 % decrease, P<0.05). This is the first report demonstrating centhaquin citrate antinociception and its blockade by BRL-44408 and imiloxan. We conclude that ¦Á_2A and ¦Á_2B but not ¦Á_2C adrenoceptors are involved in centhaquin antinociception in mice.