title: Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides μ1 receptor-mediated post-ictal antinociception.
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.
  
  
  BACKGROUND
  This study characterizes the effect of a dendrimer-naloxonazine complex on μ1 receptor-mediated post-ictal antinociception in an animal model of seizure disorder.
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto School of Medicine of University of São Paulo, Ribeirão Preto (SP), Brazil.
authors.forename: Tatiana Tocchini
authors.initials: TT
authors.lastname: Felippotti
authors.forename: Devaney Ribeiro
authors.initials: DR
authors.lastname: do Carmo
authors.forename: Leonardo Lataro
authors.initials: LL
authors.lastname: Paim
authors.forename: Nelson Ramos
authors.initials: NR
authors.lastname: Stradiotto
authors.forename: Urquisa de Oliveira
authors.initials: Ude O
authors.lastname: Bicalho
authors.forename: Carlos Amílcar
authors.initials: CA
authors.lastname: Parada
authors.forename: Renato
authors.initials: R
authors.lastname: Grillo
authors.forename: Leonardo Fernandes
authors.initials: LF
authors.lastname: Fraceto
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000698:Analgesia; D000818:Animals; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D010433:Pentylenetetrazole; D011126:Polypropylenes / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced
chemical_list: C506111:DAB-Am-16; D050091:Dendrimers; D004337:Drug Carriers; D009292:Narcotic Antagonists; D011126:Polypropylenes; D017450:Receptors, Opioid, mu; D009270:Naloxone; C034643:naloxonazine; D010433:Pentylenetetrazole