TY  - JOUR
AB  - © 2017 American Chemical Society. It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 ?M and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 ?M. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors.
AU  - Mostyn, SN
AU  - Carland, JE
AU  - Shimmon, S
AU  - Ryan, RM
AU  - Rawling, T
AU  - Vandenberg, RJ
DA  - 2017/09/20
DO  - 10.1021/acschemneuro.7b00105
EP  - 1959
JO  - ACS Chemical Neuroscience
PY  - 2017/09/20
SP  - 1949
TI  - Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2
VL  - 8
Y1  - 2017/09/20
Y2  - 2026/07/08
ER  -