A novel orally active group 2 metabotropic glutamate receptor agonist: LY354740.
Non-specific metabotropic glutamate receptor (mGluR) agonists have previously been shown to potentiate responses of spinal neurones to ionotropic glutamate receptor agonists. In this study we show that LY354740, which is a highly selective Group 2 mGluR agonist with nanomolar potency in vitro, also mimics the above effects following local ejection on spinal neurones in vivo, an action which is blocked by a Group 2 antagonist. Despite its polar nature, LY354740 is also active given either by the i.v. or the oral route (2.5-20 mg/kg) and thus will be a useful agent for investigating the role of Group 2 mGluRs both physiologically and clinically.
Bond
A
A
Lilly Research Centre, Surrey, UK.
Monn
J A
JA
Lodge
D
D
D000284:Administration, Oral; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007478:Iontophoresis; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C104753:eglumetad