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Updated: Jun 19, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Interaction of morphine with a new alpha2-adrenoceptor agonist in mice
Roberto T Sudo1, Jorge A Calasans-Maia, Suely L Galdino
1Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil. rtsudo@farmaco.ufrj.br
Unlabelled:
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 alpha(2)-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 alpha(2)-adrenoceptors, and by BRL 44408, a selective alpha(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 alpha(2A)-adrenoceptor.
Perspective:
This study introduces a new analgesic compound (PT-31) that acts via alpha(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.
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