Interaction of Morphine With a New α₂-Adrenoceptor Agonist in Mice

详细信息    查看全文

• 作者：Roberto T. Sudo ; Jorge A. Calasans-Maia ; Suely L. Galdino ; Maria C.A. Lima ; Gisele Zapata-Sudo ; Marcelo Z. Hern ; es ; Ivan R. Pitta
• 关键词：α ; ₂-adrenoceptor agonist ; antinociception ; morphine ; imidazolidine
• 刊名：The Journal of Pain
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：11
• 期：1
• 页码：71-78
• 全文大小：688 K

文摘

Finding new chemicals or adjuvants with analgesic effects in the central nervous system is clinically relevant due to the limited number of drugs with these properties. Here, we present PT-31, which is chemically related to 3-benzyl-imidazolidine, with an analgesic profile that results from α₂-adrenoceptor activation. Intraperitoneal administration of PT-31 dose-dependently produced antinociception in the hot plate test, and interacted synergistically with morphine. This effect was completely reversed by yohimbine, a non-selective antagonist of α₂-adrenoceptors, and by BRL 44408, a selective α_2A-adrenoceptor antagonist. The combination of morphine and PT-31 produced greater antinociceptive activity than either alone, and isobolographic analysis revealed a synergistic interaction between these compounds. Docking results confirm the high affinity of the PT-31 ligand at the α_2A-adrenoceptor.

Perspective

This study introduces a new analgesic compound (PT-31) that acts via α_2A-adrenoceptor activation. A significant increase in analgesia was observed when co-administered with morphine. PT-31 is an interesting new substance for pain therapy.