Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers

• Published in: Pain (Amsterdam) Vol. 155; no. 5; pp. 929 - 936
• Main Authors: Petersen, Karin L., Iyengar, Smriti, Chappell, Amy S., Lobo, Evelyn D., Reda, Haatem, Prucka, William R., Verfaille, Steven J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.05.2014; International Association for the Study of Pain; Elsevier
• Subjects: Adult; Analgesic; Analgesics; Antihyperalgesic; Biological and medical sciences; Brief thermal stimulation model; Cross-Over Studies; Double-Blind Method; Efficacy; Excitatory Amino Acid Antagonists - adverse effects; Excitatory Amino Acid Antagonists - pharmacokinetics; Excitatory Amino Acid Antagonists - therapeutic use; Female; Healthy Volunteers; Human experimental pain model; Humans; Hyperalgesia; Ionotropic glutamate receptor 5 receptor antagonist; Isoquinolines - adverse effects; Isoquinolines - pharmacokinetics; Isoquinolines - therapeutic use; Male; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropharmacology; Pain - drug therapy; Pharmacology. Drug treatments; Prodrugs - adverse effects; Prodrugs - pharmacokinetics; Prodrugs - therapeutic use; Tetrazoles - adverse effects; Tetrazoles - pharmacokinetics; Tetrazoles - therapeutic use; Treatment Outcome; Young Adult; Antihyperalgesic; Analgesic; Human experimental pain model; Brief thermal stimulation model; Efficacy; Ionotropic glutamate receptor 5 receptor antagonist; Hyperalgesia; Human; Ionotropic receptor; Nervous system diseases; Healthy subject; Stimulation; Glutamate receptor; Pain; Models; Antagonist; Safety; Pharmacokinetics; Biological receptor

In a 2-part study in healthy volunteers, we first established a maximally tolerated multiple dose of LY545694 of 25mg twice daily and subsequently demonstrated antihyperalgesic effect using effects in the brief thermal stimulation experimental pain model. The antihyperalgesic effect was similar to t...