Effect of a DAB-Am-16/naloxonazine nanocomplex on endogenous opioid peptides µ1 receptor-mediated post-ictal antinociception
Norberto Cysne Coimbra
Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto (SP), Brazil, Institute for Neuroscience and Behaviour (INeC), Ribeirão Preto (SP), Brazil
Abstract:
Dendrimers has been widely explored for biomedical applications. The blockade of µ1-endogenous opioid peptides receptors with naloxonazine in experimental neurology has a long-lasting effect but only after at least 24h of delay. This work aimed to obtain preliminary information about the capacity of the dendrimer DAB-Am-16 used as a drug carrier to reduce the time of pharmacological action of naloxonazine on the µ1-opioid receptor. In this context, the effect of DAB-Am-16/naloxonazine nanocomplex (DNC) was used in an experimental model of tonic-clonic seizures induced by pentylenetetrazole (PTZ). Male Wistar albino rats had their nociceptive thresholds measured by the tail-flick test. Convulsions were followed by increase of the tail-flick latencies. The intraperitoneal acute pre-treatment with DNC, but not with naloxonazine alone, antagonized the post-ictal antinociception (PIA) as compared with the control. Furthermore, after the long-lasting treatment, although naloxonazine alone decreased the PIA, DNC failed in antagonizing the tonic-clonic seizure-induced antinociception. According to the Racine’s index, there is no intrinsic influence exerted by neither acutely nor chronically administered naloxonazine, DAB-Am-16 dendrimer nor DNC on the characteristics of seizures. These findings suggest that nanostructured associations of DAB-Am-16 and naloxonazine can optimize the acute effect of the m1-opioid receptor blockade in experimental models of epilepsy.
