Effects of a metabotropic glutamate2/3 receptor agonist (LY544344/LY354740) on panic anxiety induced by cholecystokinin tetrapeptide in healthy humans: preliminary results
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Preclinical findings have repeatedly shown an anxiolytic-like action of agonists at metabotropic glutamate receptors type II, such as LY354740.
We aimed to investigate the effect of LY544344, the prodrug of LY354740, upon experimental panic anxiety in humans.
Twelve healthy human volunteers were treated orally with 80 mg bid LY544344 for 1 week in a randomized placebo-controlled cross-over study before 50 μg cholecystokinin tetrapeptide (CCK-4) was injected intravenously. We assessed CCK-induced panic and anxiety symptoms and measured stress hormone release.
While no significant treatment effect emerged in the entire sample, a significant reduction of the number of CCK-4-induced panic symptoms and of CCK-4-induced subjective anxiety ratings was detected after removing two subjects who did not show decreased CCK-4-elicited adrenocorticotropin (ACTH) release after LY544344 compared to placebo treatment.
Further studies are needed to clarify the potential of LY544344 as a new anxiolytic or antipanic drug.
KeywordsMetabotropic glutamate receptors CCK-4 Panic Anxiety LY544344 ACTH Cortisol Prolactin
This investigation was supported by Eli Lilly and Company, Indianapolis, Ind., USA. We thank Peter R. Bieck (Lilly Corporate Center, Indianapolis, Ind., USA) for his friendly help to provide us with LY544344, Mrs. Anneliese Mästele (Lilly Deutschland GmbH, Bad Homburg, Germany) for her outstanding administrative support, and Ms. Claudia Vergien and Mrs. Iris Remmlinger-Marten for their expert technical assistance. This study is part of the MD thesis of Ms. Kristina Stark.
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