Effects of a metabotropic glutamate(2/3) receptor agonist (LY544344/LY354740) on panic anxiety induced by cholecystokinin tetrapeptide in healthy humans: preliminary results.
BACKGROUND
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.
Kellner
Michael
M
Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. kellner@uke.uni-hamburg.de
Muhtz
Christoph
C
Stark
Kristina
K
Yassouridis
Alexander
A
Arlt
Josef
J
Wiedemann
Klaus
K
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001007:Anxiety / Q000188:drug therapy*; D001643:Bridged Bicyclo Compounds / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D016584:Panic Disorder / Q000188:drug therapy*; D011388:Prolactin / Q000097:blood; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013758:Tetragastrin / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D013758:Tetragastrin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; C104753:eglumetad; D006854:Hydrocortisone