Reversible inhibition of the glycine transporter GlyT2 circumvents acute toxicity while preserving efficacy in the treatment of pain.

ABSTRACT:

Background and purpose

Available medications for chronic pain provide only partial relief and often cause unacceptable side effects. There is therefore a need for novel molecular targets to develop new therapeutics with improved efficacy and tolerability. Despite encouraging efficacy data in rodents with inhibitors of the neuronal glycine transporter-2 (GlyT2), there are also some reports of toxicity and their development was discontinued.

Experimental approach

In order to clarify the possibility of targeting GlyT2 for the treatment of pain, we have used an integrated approach comprising in vitro pharmacology, selectivity, bioavailability, in vivo efficacy and safety assessment to analyse the properties and efficacy of ALX-1393 and Org-25543, the two published GlyT2 inhibito

SUBMITTER: Mingorance-Le Meur A 

PROVIDER: S-EPMC3949653 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature