Gyógyszerészet, farmakogenomika, gyógyszerkutatás és tervezés, gyógyszeres kezelés
The current pharmacological approach for the treatment of opioid use disorder (OUD),
as a result of prescription misuse or illicit opioids, utilises opioid ligands that
have either an agonist or antagonist profile. In this context, methadone and buprenorphine
act as opioid agonists, whereas naltrexone functions as an opioid antagonist. To decrease
the reinforcing effects of illicit opioids, higher doses of methadone and buprenorphine
have been recommended, but this is associated with increased side effects. Therefore,
several preclinical efforts have been carried out over the last decades to find drugs
that act on receptors other than opioid receptors. A large body of preclinical evidence
has shown the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists like ketamine
to treat opioid addiction behaviours in animals. Indeed, ketamine by itself is an
addictive drug; thus, the treatment of OUD is still a matter to be solved. Growing
data position glycine transporter 1 as a possible therapeutic target for the treatment
of substance use disorder. This transporter regulates the reuptake of glycine, which
can modulate the function of both NMDARs and GPR158, a metabotropic glycine receptor
(mGlyR); thus, it is worth investigating in the management of OUD. To gain insight
into the role of glycinergic transmission in OUD, alongside NMDAR-mediated glutamatergic
transmission, dopaminergic and GABAergic transmission were also reviewed.
