Effects of a metabotropic glutamate(2/3) receptor agonist (LY544344/LY354740) on panic anxiety induced by cholecystokinin tetrapeptide in healthy humans: preliminary results

Rationale: Preclinical findings have repeatedly shown an anxiolytic-like action of agonists at Metabotropic Glutamate Receptors type II, such as LY354740.

Objective: We aimed to investigate the effect of LY544344, the prodrug of LY354740, upon experimental panic anxiety in humans.

Methods: 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 mug cholecystokinin tetrapeptide (CCK-4) was injected intravenously. We assessed CCK-induced panic and anxiety symptoms and measured stress hormone release.

Results: 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.

Conclusions: Further studies are needed to clarify the potential of LY544344 as a new anxiolytic or antipanic drug.