The Journal of Pain
Volume 11, Issue 1 , Pages 71-78, January 2010

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

  • Roberto T. Sudo

      Affiliations

    • Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
    • Corresponding Author InformationAddress reprint requests to Dr. Roberto T. Sudo, Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Bloco J, Sala 14, Rio de Janeiro, Brazil, CEP 21941-590.
    • ,
  • Jorge A. Calasans-Maia

      Affiliations

    • Serviço de Anestesiologia e Programa de Pós-Gradução em Medicina (Cirurgia), Universidade Federal do Rio de Janeiro, Brazil
    • ,
  • Suely L. Galdino

      Affiliations

    • Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Brazil
    • ,
  • Maria C.A. Lima

      Affiliations

    • Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Brazil
    • ,
  • Gisele Zapata-Sudo

      Affiliations

    • Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
    • ,
  • Marcelo Z. Hernandes

      Affiliations

    • Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Brazil
    • ,
  • Ivan R. Pitta

      Affiliations

    • Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Brazil

Received 9 March 2009; received in revised form 8 July 2009; accepted 4 August 2009. published online 23 October 2009.

Abstract 

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 α2A-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 α2A-adrenoceptor.

Perspective

This study introduces a new analgesic compound (PT-31) that acts via α2A-adrenoceptor activation. A significant increase in analgesia was observed when co-administered with morphine. PT-31 is an interesting new substance for pain therapy.

Key words: α2-adrenoceptor agonist, antinociception, morphine, imidazolidine

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, BR), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BR), Fundação Universitária Jose Bonifácio (FUJB, BR), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, BR) and Instituto do Milênio: Inovação e Desenvolvimento de Fármacos e Medicamentos – IM-INOFAR for finantial support and fellowships.

PII: S1526-5900(09)00662-2

doi:10.1016/j.jpain.2009.08.001

The Journal of Pain
Volume 11, Issue 1 , Pages 71-78, January 2010

Article Tools

* Image Usage & Resolution