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 µ(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 µ1 receptor-mediated post-ictal antinociception in an animal model of seizure disorder.
