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.
RCT Entities:
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.
Authors: J A Monn; M J Valli; S M Massey; R A Wright; C R Salhoff; B G Johnson; T Howe; C A Alt; G A Rhodes; R L Robey; K R Griffey; J P Tizzano; M J Kallman; D R Helton; D D Schoepp Journal: J Med Chem Date: 1997-02-14 Impact factor: 7.446
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