Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides mu(1) receptor-mediated post-ictal antinociception

Author(s)

Felippotti, Tatiana Tocchini ^{[1, 2]} ; do Carmo, Devaney Ribeiro ^[3] ; Paim, Leonardo Lataro ^[3] ; Stradiotto, Nelson Ramos ^[4] ; Bicalho, Urquisa de Oliveira ^[3] ; Parada, Carlos Amilcar ^[5] ; Grillo, Renato ^[6] ; Fraceto, Leonardo Fernandes ^[6] ; Coimbra, Norberto Cysne ^{[1, 2]}

Affiliation

^[1] Inst Neurosci & Behav INeC, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049 Ribeirao Preto, SP - Brazil

^[3] UNESP, Ilha Solteira Sch Engn, Dept Phys & Chem, Ilha Solteira, SP - Brazil

^[4] UNESP, Inst Chem Araraquara, Dept Analyt Chem, Araraquara, SP - Brazil

^[5] Univ Estadual Campinas, UNICAMP, Dept Physiol & Biophys, Inst Biol, Campinas, SP - Brazil

^[6] UNESP, Dept Environm Engn, Sorocaba, SP - Brazil

• Document type: Journal article
• Source: Nanomedicine-Nanotechnology Biology and Medicine; v. 7, n. 6, p. 871-880, DEC 2011.
• Web of Science Citations: 13

Abstract

The aim of this study was to investigate the capacity of the host dendrimer DAB-Am-16 as a drug carrier to reduce the time required for the encapsulated naloxonaxine to establish an irreversible covalent bond with mu(1)-opioid receptor (resulting in a pharmacologically selective effect). The efficacy of dendrimer-naloxonazine nanocomplex (DNC) was studied in antinociception induced by convulsions elicited by intraperitoneal (IP) administration of pentylenetetrazole, and analgesia was measured by the tail-flick test. We found that animals showed increased tail-flick latencies following convulsions. Furthermore, acute pre-treatment (10 minutes) with DNC, but not with naloxonazine alone, antagonized post-ictal analgesia in comparison with control pre-treatment. However, naloxonazine treatment 24 hours before PTZ decreased post-ictal antinociception, but DNC failed to antagonize tonic-clonic seizure-induced analgesia. In addition, according to Racine's index of seizure severity, naloxonazine, DAB-Am-16 dendrimer or DNC did not influence seizure severity when administered either 10 minutes or 24 hours before PTZ. From the Clinical Editor: This study characterizes the effect of a dendrimer-naloxonazine complex on mu(1) receptor-mediated post-ictal antinociception in an animal model of seizure disorder. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/00668-6 - Study of the involvement of cholinergic pathways form tegmentar pedunculopontine nucleus to monoaminergic nuclei of the pain endogenous inhibitory system in the post-ictal antinociception
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants