Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers.
Vigabatrin increases gamma aminobutyric acid (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T). Preclinical studies suggest anxiolytic effects in vigabatrin treated rats. Anxiolytic effects in patients with panic disorder (PD) could therefore be expected. To evaluate putative anxiolytic properties of vigabatrin in humans, CCK-4-induced panic symptoms were studied in healthy volunteers before and after vigabatrin treatment. After placebo-controlled administration of 50 microg CCK-4, ten healthy volunteers received vigabatrin for seven days with a daily dosage of 2 g. The treatment period was followed by a second CCK-4 challenge. Panic and anxiety were assessed using the Acute Panic Inventory (API) score and a DSM-IV derived panic-symptom-scale (PSS). ACTH and cortisol plasma levels were determined during the CCK-4 challenge. All subjects reported a marked reduction of CCK-4-induced panic symptoms and anxiety after seven days of vigabatrin treatment both in the API- and PSS-scores. Moreover, there was a significant attenuation of CCK-induced elevation of ACTH and cortisol levels following vigabatrin treatment. In conclusion, our data show that GABA-transaminase inhibitors exert anxiolytic effects in CCK-4-induced panic in healthy volunteers and suggest that GABA transaminase inhibitors might be useful in ameliorating panic symptoms also in patients with PD.
Zwanzger
P
P
Department of Psychiatry, University of Munich, Nussbaumstrasse 7, 80336 Munich, Germany. zwanzger@psy.med.uni-muenchen.de
Baghai
T C
TC
Schuele
C
C
Ströhle
A
A
Padberg
F
F
Kathmann
N
N
Schwarz
M
M
Möller
H J
HJ
Rupprecht
R
R
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010200:Panic / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D013758:Tetragastrin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D020888:Vigabatrin / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D013758:Tetragastrin; D000324:Adrenocorticotropic Hormone; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D006854:Hydrocortisone