Different Effects of Anxiolytics Phenazepam and Fabomotizole on Dipeptidylpeptidase-IV Plasma Activity in Patients with Anxiety Disorders T
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P.4.a.006 Different effects of anxiolytics phenazepam and fabomotizole on dipeptidylpeptidase-IV plasma activity in patients with anxiety disorders T. Syunyakov1, N. Zolotov2, G. Neznamov1. ZAKUSOV INSTITUTE OF PHARMACOLOGY; Moscow, Russia 1 Laboratory of Clinical Psychopharmacology; 2 Laboratory of Psychopharmacology Background: Results: Dipeptidylpeptidase-IV (DPP-4) is the enzyme that has: membrane-fixed and shed circulating form • Patients with anxiety disorders has both changed plasma concentration and plasma activity of DPP-4 comparing to healthy control [1]. • These changes may reflect underlying mechanisms of anxiety and stress on the cell membrane. • Classical benzodiazepine (phenazepam) and atypical σ1-agonist Fabomotizole treatment was not associated with significant changes of anxiolytic (fabomotizole) may have different effects on the DPP- the mean DPP-4 plasma activity (mean changes 0.03 ± 1.37 from 5.32 IV anchoring and plasma activity in patients with anxiety ± 1.13 ng/ml/min to 5.39 ± 1.09, p > 0.05), while phenazepam disorders. treatment lead to a significant DPP-4 activity reduction (−0.79 ± 1.13 Aim of the Study: To probe how the DPP-IV plasma activity changes from 4.84 ± 1.29 to 4.05 ± 1.04 ng/ml/min, p < 0.01). Between-drug during treatment with anxiolytics with distinct mechanisms of action. differences in the DPP-4 activity changes (F = 6.06, p = 0.012). Methods: For this study we used anxiolitycs fabomotizole and DPP-4 plasma activity changes during phenazepam and phenazepam that has distinct mechanisms of action. Fabomotizole fabomotizole treatment bind to σ1-receptors and prevent stress-induced drop in benzodiazepine site of GABA-A receptors binding capability. Phenazepam is a typical benzodiazepine anxiolytic. Phenazepam lead to the decrease of DPP-4 activity in Fabomotizole 33 out of 36 patients Fabomotizole decreased its DPP-4 activity DPP-4 activity activity in 28 patients and Day 1 Day 14 increased in 22 patients Phenazepam (Yates corrected χ2 = 11.24, p < 0.001). DPP-4 plasma activity was using the method described elsewhere [1]. Control group consisted of 32 healthy volunteers. Statistical analysis of the plasma DPP-4 activity changes included two-way ANOVA with DPP-4 plasma activity as the dependent variable and drug as an independent predictor. All statistical tests were Changes of DPP-4 activity in patients in the fabomotizole group was two tailed, and p-values < 0.05 were considered significant. significantly dependent on the background activity: an increase occurred in patients with lower and decrease with higher background levels. Mean activity in patients with decrease was 5.88 ± 0.93 and in Fabomotizole Phenazepam Overall N=50 N=36 N=86 patients with increase 4.76 ± 1.06 ng/ml/min (p < 0.05). n=50 n=36 n=86 Age, years * 34,44 (10,29) 35,83 (10,23) 35,13 (10,21) 30 (60,0%) Conclusion: Women, n (%) ** 23 (63,9%) 53 (61,6%) GAD** 15 (30,0%) 10 (27,8%) 25 (29,1%) • Plasma DPP-IV activity in patients with anxiety disorders is increased comparing to healthy control. Nosophobia** 17 (34,0%) 13 (36,1%) 30 (34,9%) • Anxiolytics with distinct mechanisms lead to different patterns of Agoraphobia** 18 (36,0%) 13 (36,1%) 31 (36,0%) DPP-4 activity changes. • If DPP-4 in anxiety disorders linked to disturbed anchoring on the cell Disease duration* 23,52 (32,68) 32,66 (43,40) 27,67 (37,94) membrane than observed different effects may be accounted for different mechanisms of action of both anxiolytics on the cell * Mean (SD) membrane. ** n (%) [1] Zolotov N.N., Syunyakov T.S., Dorofeeva O.A. et al. Activity of prolyn-specific enzymes in patients with anxiety disorders and its changes during phenazepam’ treatment. Psychiatry and Psychopharmacotherapy. 2012; 6: 4-7 Copyright © 2017 T. Syunyakov, N. Zolotov, G. Neznamov [email protected] .