Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects.

ABSTRACT: Several investigations into the sites of action of opioid analgesics have utilized peripherally acting mu-opioid receptor antagonists (PAMORAs), which have been incorrectly assumed to possess limited permeability across the blood-brain barrier. Unfortunately, the poor pharmacokinetic properties of current PAMORAs have resulted in misunderstandings of the role of central nervous system and gastrointestinal tract in precipitating side effects such as opioid-induced constipation. Here, we develop a drug delivery approach for restricting the passage of small molecules across the blood-brain barrier. This allows us to develop naloxone- and oxycodone-based conjugates that display superior potency, peripheral selectivity, pharmacokinetics, and efficacy in rats compared to other clinically used PA

SUBMITTER: Tuhin MTH 

PROVIDER: S-EPMC9226319 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature