Effects of different ischemic pressures on bar velocity during the bench press exercise: A randomized crossover trial.

The main objective of this study was to evaluate the effects of different ischemic pressures applied during rest intervals on bar velocity during the bench press exercise. 10 resistance-trained males (age = 23.2 ± 2.7 years; body mass = 83.9 ± 9 kg; body height = 181 ± 5.2 cm; bench press 1 repetition maximum (1RM) = 125 ± 16.4 kg; training experience = 5.4 ± 3.4 years) participated in the study. During 4 experimental sessions, following a randomized crossover design, the subjects performed 5 sets of 3 repetitions of the bench press exercise with a load of 60% 1RM under conditions: with ischemia (50% or 80% of arterial occlusion pressure), with SHAM ischemia (20 mmHg) and without ischemia (control condition). For the ischemic conditions cuffs were applied before each set for 6.5 min and released 30 s before the start of the set as reperfusion (6.5 min ischemia + 0.5 min reperfusion). In the control condition, ischemia was not applied. The two-way repeated measures ANOVA showed no significant condition × set interaction for mean bar velocity (MV; p = 0.17) and peak bar velocity (PV; p = 0.66). There was also no main effect of condition for MV (p = 0.58) and PV (p = 0.61). The results indicate that ischemic or SHAM treatment (6.5 minutes ischemia or SHAM + 30 s reperfusion) does not affect mean and peak bar velocity during the bench press exercise regardless of the applied pressure.

Will Music Give Me Power? Effects of Listening to Music during Active and Passive Rest Intervals on Power Output during Resistance Exercise.

The study aimed to evaluate the impact of listening to preferred music during active/passive rest on power output and heart rate in barbell squats (BS) and bench presses (BP). Fifteen participants (13 males and 2 females), moderately resistance trained, were engaged in four randomized experimental sessions with varying rest intervals (active/passive) and music presence (listening or not). Each session involved three sets of three repetitions of BS and BP at a 50% one-repetition maximum. ANOVA showed a significant main effect of the set for BP relative mean and peak power output (p < 0.001; both). The post hoc comparisons indicated a significantly higher BP relative mean and peak power output in set_2 (p < 0.001; effect size [ES] = 0.12 and p < 0.001; ES = 0.10) and set_3 (p < 0.001; ES = 0.11 and p = 0.001; ES = 0.16) in comparison to set_1. Moreover, a main effect of the set indicating a decrease in BS relative peak power output across sets was observed (p = 0.024) with no significant differences between sets. A significantly higher mean heart rate during active rest in comparison to passive rest was observed (p = 0.032; ES = 0.69). The results revealed no significant effect of listening to music on relative power output and heart rate during BS and BP.

Effects of blood flow restriction on mechanical properties of the rectus femoris muscle at rest.

Introduction: This study examined the effects of blood flow restriction (BFR) and reperfusion on the mechanical properties of the rectus femoris muscle at rest (frequency and stiffness). Methods: Fourteen trained men (body weight = 81.0 ± 10.3 kg; BMI = 25 ± 3.0 m/kg2; height = 181 ± 4 cm; training experience = 6.0 ± 2.2 years) participated in an experimental session involving their dominant (BFR) and non-dominant leg (control). Muscle mechanical properties were measured using Myoton's accelerometer at the midpoint of the rectus femoris muscle at five time points. In the BFR leg, an 80% arterial occlusion pressure was applied by a cuff for 5 min. No cuff was applied in the control leg. Femoral Myoton measurements were taken from both legs 2 and 4 min after the start of BRF as well as 30 s and 2 min after the end of the occlusion period. Results: The two-way ANOVA revealed a statistically significant interaction effect for stiffness and frequency (p < 0.001; η2 > 0.67). The post hoc analysis showed that both stiffness and frequency increased during BFR compared with rest and then dropped to the resting levels post BFR period. Also, stiffness and frequency were higher than control only during the BFR period, and similar during rest and post BFR. Conclusion: These results indicate that the application of BFR at rest leads to significant changes in mechanical properties of the rectus femoris muscle.

Effects of Flywheel vs. Free-Weight Squats and Split Squats on Jumping Performance and Change of Direction Speed in Soccer Players.

The objective of this study was to compare (i) The effects of a flywheel and free-weight resistance training program; and (ii) The effects of performing lateral and frontal split squats as part of a flywheel-resistance training program on jumping performance, the 5-0-5 change of direction test time, and the one-repetition maximum (1RM) back squat in soccer players. Twenty-four male amateur soccer players participated in this study and were randomly and equally assigned to one of three different test groups: forward split-squat group (FSQ); lateral split-squat group (LSQ); and free-weight training group (TRAD). Athletes in the FSQ group performed a squat and a forward split squat on a flywheel device, while those in the LSQ group performed a squat and a lateral split squat (instead of a forward split squat) on a flywheel device. Each training lasted 4 weeks. The main finding was that all training groups, such as TRAD, FSQ, and LSQ, significantly improved broad jump length (p = 0.001; effect size [ES] = 0.36), 5-0-5 COD time with a turn on the dominant limb (p = 0.038; ES = 0.49), and 1RM back squat (p = 0.001; ES = 0.4). In turn, both flywheel-resistance training groups (FSQ and LSQ) significantly improved their counter-movement jump height (p = 0.001; ES = 0.8 and p = 0.002; ES = 0.58; respectively) with no effect in the TRAD (p = 0.676; ES = 0.07) training group. Both free-weight and flywheel-resistance training lasting 4 weeks performed in-season contributed to significant improvement in 1RM back squat, broad jump performance, and 5-0-5 change of direction testing time, while flywheel-resistance training might be superior in counter-movement jump height enhancement in soccer players. Moreover, the manner in which split squats were performed was not a factor influencing the obtained results.

Resistance Training with Blood Flow Restriction and Ocular Health: A Brief Review.

Despite the many health benefits of resistance training, it has been suggested that high-intensity resistance exercise is associated with acute increases in intraocular pressure which is a significant risk factor for the development of glaucomatous optic nerve damage. Therefore, resistance training using a variety of forms (e.g., resistance bands, free weights, weight machines, and bodyweight) may be harmful to patients with or at risk of glaucoma. An appropriate solution for such people may involve the combination of resistance training and blood flow restriction (BFR). During the last decade, the BFR (a.k.a. occlusion or KAATSU training) method has drawn great interest among health and sports professionals because of the possibility for individuals to improve various areas of fitness and performance at lower exercise intensities. In comparison to studies evaluating the efficiency of BFR in terms of physical performance and body composition changes, there is still a paucity of empirical studies concerning safety, especially regarding ocular health. Although the use of BFR during resistance training seems feasible for glaucoma patients or those at risk of glaucoma, some issues must be investigated and resolved. Therefore, this review provides an overview of the available scientific data describing the influence of resistance training combined with BFR on ocular physiology and points to further directions of research.

Ischemia during rest intervals between sets prevents decreases in fatigue during the explosive squat exercise: a randomized, crossover study.

The study aimed to evaluate the impact of ischemia, used only before particular sets of a lower limb resistance exercise on power output. Ten healthy resistance-trained males (age = 26 ± 6 years; body mass = 90 ± 9 kg; training experience = 9 ± 7 years) performed two experimental sessions (with ischemia; control without ischemia) following a randomized crossover design. During the ischemic condition, the cuffs were inflated to 60% of arterial occlusion pressure. The cuffs were applied before each set for 4.5 min and released 30 s before the start of the set as the reperfusion (4.5 min ischemia + 0.5 min reperfusion). In the control condition, ischemia was not applied. During the experimental sessions, the subjects performed the Keiser machine squat exercise protocol which consisted of 5 sets of two repetitions, at a load of 60% of one-repetition maximum (1RM), with 5 min rest intervals between sets. The repetitions were performed with maximal velocity. The two-way repeated-measures ANOVA showed a statistically significant interaction effect for power output (p < 0.01; η2 = 0.26). There was also a statistically significant main effect of condition for power output (p = 0.02; η2 = 0.40). The post hoc analysis for interaction did not show significant differences between conditions in particular sets. The post hoc analysis for the main effect of the condition revealed that power output was significantly lower in the control group compared to the group where ischemic was used (p = 0.02). The t-test comparisons for particular sets showed a significant lower power output in set 3 (p = 0.03); set 4 (p < 0.01) and set 5 (p < 0.01) for the control condition when compared to the ischemic condition. The results indicate that ischemia applied before each set and released 30 s prior to the start of the squat exercise did not increase power output performance. However, we observed a significantly lower decline in power for the ischemic condition (4.5 min ischemia + 0.5 min reperfusion) in sets 3-5 compared to the control condition. Thus repeated ischemia with reperfusion used between sets can be an effective form of performance enhancement by preventing or at least diminishing fatigue during resistance exercise.

Impact of Movement Tempo Distribution on Bar Velocity During a Multi-Set Bench Press Exercise.

The goal of the present study was to evaluate the effect of contrast tempo movement on bar velocity changes during a multi-set bench press exercise. In randomized and counter-balanced order, participants performed three sets of the bench press exercise at 60%1RM under two testing conditions: E-E where all repetitions were performed with explosive (X/0/X/0) movement tempo; and S-E where the first two repetitions were performed with a slow tempo (5/0/X/0) while the third repetition was performed with explosive movement tempo (slow, slow, explosive). Twelve healthy men volunteered for the study (age = 30 ± 5 years; body mass = 88 ± 10 kg; bench press 1RM = 145 ± 24 kg). The three-way repeated measures ANOVA (tempo × set × repetition) showed statistically significant multi-interaction effect for peak bar velocity (p < 0.01; η2 = 0.23), yet not for mean bar velocity (p = 0.09; η2 = 0.14). The post hoc results for multi-interaction revealed that peak bar velocity in the 3rd repetition was significantly higher for E-E compared to SE only during set 1 (p < 0.001). Therefore, the distribution of movement tempo had a significant impact on peak bar velocity, but not on mean bar velocity. The decrease in peak bar velocity in the 3rd repetition during the S-E condition was observed only in the first set, while such a tendency was not observed in the second and third set.

Acute impact of blood flow restriction on strength-endurance performance during the bench press exercise.

The main goal of the present study was to evaluate the acute effects of blood flow restriction (BFR) at 70% of full arterial occlusion pressure on strength-endurance performance during the bench press exercise. The study included 14 strength-trained male subjects (age = 25.6 ± 4.1 years; body mass = 81.7 ± 10.8 kg; bench press 1 repetition maximum (1RM) = 130.0 ± 22.1 kg), experienced in resistance training (3.9 ± 2.4 years). During the experimental sessions in a randomized crossover design, the subjects performed three sets of the bench press at 80% 1RM performed to failure with two different conditions: without BFR (CON); and with BFR (BFR). Friedman's test showed significant differences between BFR and CON conditions for the number of repetitions performed (p < 0.001); for peak bar velocity (p < 0.001) and for mean bar velocity (p < 0.001). The pairwise comparisons showed a significant decrease for peak bar velocity and mean bar velocity in individual Set 1 for BFR when compared to CON conditions (p = 0.01 for both). The two-way repeated measures ANOVA showed a significant main effect for the time under tension (p = 0.02). A post-hoc comparisons for the main effect showed a significant increase in time under tension for BFR when compared to CON (p = 0.02). The results of the presented study indicate that BFR used during strength-endurance exercise generally does not decrease the level of endurance performance, while it causes a drop in bar velocity.

The Effects of Ischemia During Rest Intervals on Bar Velocity in the Bench Press Exercise With Different External Loads.

The main aim of the present study was to evaluate the acute effects of ischemia used during rest periods on bar velocity changes during the bench press exercise at progressive loads, from 20 to 90% of 1RM. Ten healthy resistance trained men volunteered for the study (age = 26.3 ± 4.7 years; body mass = 89.8 ± 6.3 kg; bench press 1RM = 142.5 ± 16.9 kg; training experience = 7.8 ± 2.7 years). During the experimental sessions the subjects performed the bench press exercise under two different conditions, in a randomized and counterbalanced order: (a) ischemia condition, with ischemia applied before the first set and during every rest periods between sets, and (b) control condition where no ischemia was applied. During each experimental session eight sets of the bench press exercise were performed, against loads starting from 20 to 90% 1RM, increased progressively by 10% in each subsequent set. A 3-min rest interval between sets was used. For ischemia condition the cuffs was applied 3 min before the first set and during every rest period between sets. Ischemia was released during exercise. The cuff pressure was set to ∼80% of full arterial occlusion pressure. The two-way repeated measures ANOVA showed a statistically significant interaction effect for peak bar velocity (p = 0.04) and for mean bar velocity (p = 0.01). There was also a statistically significant main effect of condition for peak bar velocity (p < 0.01) but not for mean bar velocity (p = 0.25). The post hoc analysis for interaction showed significantly higher peak bar velocity for the ischemia condition compared to control at a load of 20% 1RM (p = 0.007) and at a load of 50% 1RM (p = 0.006). The results of the present study indicate that ischemia used before each set even for a brief duration of <3 min, has positive effects on peak bar velocity at light loads, but it is insufficient to induce such effect on higher loads.

The Acute Post-Activation Performance Enhancement of the Bench Press Throw in Disabled Sitting Volleyball Athletes.

The purpose of the present study was to examine the acute effects of the bench press exercise with predetermined velocity loss percentage on subsequent bench press throw (BPT) performance with raised legs or feet on the floor among disabled, sitting volleyball players. Twelve elite sitting volleyball athletes (age = 33 ± 9 years; body mass = 84.7 ± 14.7 kg; relative bench press maximum strength = 1.0 ± 0.3 kg/body mass) took part in this study. The experiment was performed following a randomized crossover design, where each participant performed a single set of bench press with a 60% one-repetition maximum (1RM) to a 10% decrease of mean bar velocity as a conditioning activity (CA). The BPT with a 60%1RM was performed to assess changes in peak power (PP), peak velocity (PV) before and after the CA. The differences between analyzed variables before and after the CA were verified using two-way repeated-measures ANOVA (condition × time; 2 × 2). The ANOVA showed a significant main effect of time for peak bar velocity (p = 0.03; η2 = 0.312) and peak power output (p = 0.037; η2 = 0.294). The post hoc comparison showed a significant increase in post-CA peak bar velocity and peak power for raised legs condition in comparison with pre-CA value (p = 0.02, p = 0.041, respectively). The present study showed that the subsequent BPT performed with raised legs could be enhanced by the bench press with a 60% 1RM to a 10% mean bar velocity decrease as a CA among disabled sitting volleyball players. Therefore, athletes and coaches can consider performing a bench press throw with raised legs without compromising performance.

Corrigendum: Contrast Tempo of Movement and Its Effect on Power Output and Bar Velocity During Resistance Exercise.

[This corrects the article DOI: 10.3389/fphys.2020.629199.].

Impact of Ischemic Intra-Conditioning on Power Output and Bar Velocity of the Upper Limbs.

This study evaluated the effects of ischemic conditioning on power output and bar velocity in the bench press exercise. Ten healthy males (age: 25 ± 2 years; body mass: 92 ± 8 kg; bench press one repetition maximum -1RM: 145 ± 13 kg), took part in two experimental sessions (with and without ischemia), 1 week apart in random and counterbalanced order. In the ischemic condition, cuffs placed around the upper part of the arms were inflated to 80% of arterial occlusion pressure before each set, while in the control condition there was no blood flow restriction. The exercise protocol included 5 sets of three repetitions each, against a resistance equal to 60% 1RM, with 5 min recovery intervals between sets. There was a main effect of condition for mean power output (MP) and mean bar velocity (MV) (p = 0.01), with overall MP being higher in ischemia than in control by 5.6 ± 4.1% (mean ± 90% compatibility limits), a standardized effect size (ES) of 0.51. Overall MV was also higher by 5.5 ± 4.0%, ES = 0.63. Peak power output (PP) and peak bar velocity (PV) were similar in set 1 of the control and ischemia condition (1039 ± 105 vs. 1054 ± 82 W; 684 ± 74 vs. 696 ± 53 W; 1.09 ± 0.07 vs. 1.12 ± 0.09 m/s; 0.81 ± 0.05 vs. 0.82 ± 0.05 m/s, p = 0.67 to 0.99, mean ± standard deviation). However, from set 3 onward (p = 0.03 to 0.001), PP and PV were higher in ischemia compared with control, with the highest difference observed in set 5 (10.9 ± 5.9%, ES = 0.73 for PP and 8.6 ± 4.6%; ES = 0.89 for PV). These results indicate that ischemia used before each set of the bench press exercise increases power output and bar velocity and this may be used as performance-enhancing stimulus during explosive resistance training.

A comparison of muscle activity of the dominant and non-dominant side of the body during low versus high loaded bench press exercise performed to muscular failure.

The main aim of the study was to compare the peak surface electromyography (sEMG) amplitude of muscles during low and high loaded bench press exercises performed to muscular failure on the dominant and non-dominant body side. Ten resistance-trained healthy males with at least six-year experience in resistance training (27.7 ± 5.6 years, 81.1 ± 5.8 kg and 175.3 ± 5.2 cm, bench press one-repetition maximum [1RM] = 98.9 ± 7.1 kg) performed the bench press at 50% and at 90%1RM. The differences in peak sEMG amplitude between body-sides and the external loads were recorded for the pectoralis major (PM), anterior deltoid (AD), and the long head of the triceps brachii (TB) during each attempt. A two-way repeated-measures ANOVAs revealed statistically significant main effect of side for AD (p < 0.001) and TB (p < 0.001) but not for PM (p = 0.168) and a significant main effect of load for TB (p < 0.001) but not for AD and PM (p = 0.229; p = 0.072; respectively). The post-hoc analysis for the main effect of side showed significantly higher peak sEMG amplitude for the dominant side compared to the non-dominant side for AD and TB at 50%1RM and 90%1RM (p < 0.001; all) with no statistically significant differences for PM (p = 0.187; p = 0.155; both loads). The post-hoc analysis for the main effect of load for TB revealed a significantly higher peak sEMG amplitude at 90%1RM compared to the 50%1RM (p = 0.009). The obtained results indicate that regardless of the external load, the peak sEMG activity of the AD, PM, and TB during the bench press exercise performed to muscular failure was higher on the dominant body-side.

The Acute Impact of External Compression on Back Squat Performance in Competitive Athletes.

The aim of the present study was to evaluate the effects of external compression with blood flow restriction on power output and bar velocity changes during the back-squat exercise (SQ). The study included 10 judo athletes (age = 28.4 ± 5.8 years; body mass = 81.3 ± 13.1 kg; SQ one-repetition maximum (1-RM) 152 ± 34 kg; training experience 10.7 ± 2.3 years). METHODS: The experiment was performed following a randomized crossover design, where each participant performed three different exercise protocols: (1) control, without external compression (CONT); (2) intermittent external compression with pressure of 100% arterial occlusion pressure (AOP) (EC-100); and (3) intermittent external compression with pressure of 150% AOP (EC-150). To assess the differences between conditions, the participants performed 3 sets of 3 repetitions of the SQ at 70% 1-RM. The differences in peak power output (PP), mean power output (MP), peak bar velocity (PV), and mean bar velocity (MV) between the three conditions were examined using repeated measures two-way ANOVA. RESULTS: The post hoc analysis for the main effect of conditions showed a significant increase in PP (p = 0.03), PV (p = 0.02), MP (p = 0.04), and MV (p = 0.03), for the EC-150, compared to the CONT. Furthermore, a statistically significant increase in PP (p = 0.04), PV (p = 0.03), MP (p = 0.02), and MV (p = 0.01) were observed for the EC-150 compared to EC-100. There were no significant changes in PP, PV, MP, and MV, between EC-100 and CONT conditions. CONCLUSION: The results indicate that the use of extremely high-pressure external compression (150% AOP) during high-loaded (70% 1-RM) lower limb resistance exercise elicits an acute increase in power output and bar velocity.

Changes in Muscle Pattern Activity during the Asymmetric Flat Bench Press (Offset Training).

BACKGROUND: This study aimed to compare the muscle activity between the symmetric and selected asymmetric loads (2.5%; 5% and 7.5% differences in load position between sides of the bar) during the flat bench press (BP) exercise at 70%1RM. The study included 10 resistance-trained males (25.3 ± 2.3 years; 82.9 ± 6.9 kg; 177.8 ± 4.5 cm; 1RM BP: 104.5 ± 8.6 kg; experience: 5.6 ± 1.5 years). METHODS: To assess the differences in muscle activity between both sides of the body and load placement, the participants performed several attempts of the BP with symmetric and asymmetric load at 70%1RM in a random order (symmetric; 2.5%; 5% and 7.5% differences in load position between sides of the bar). Peak muscle activity of dominant and non-dominant body-side was recorded for the pectoralis major (PM), anterior deltoid (AD), and the long head of the triceps brachii (TB). RESULTS: A two-way repeated-measures analysis of variance (ANOVA) indicated a statistically significant main interaction between side and load (p < 0.01) for AD, PM and TB muscles. CONCLUSION: The results of this study showed that asymmetrically loaded BP leads to significantly higher muscle activity on the loaded side of the body. The offset training method during bilateral resistance exercise may be an effective and simple approach for reductions in muscle imbalances and improvement in bilateral exercise performance.

Contrast Tempo of Movement and Its Effect on Power Output and Bar Velocity During Resistance Exercise.

In this study, we examined the impact of contrast movement tempo (fast vs. slow) on power output and bar velocity during the bench press exercise. Ten healthy men (age = 26.9 ± 4.1 years; body mass = 90.5 ± 10.3 kg; bench press 1RM = 136.8 ± 27.7 kg) with significant experience in resistance training (9.4 ± 5.6 years) performed the bench press exercise under three conditions: with an explosive tempo of movement in each of three repetitions (E/E/E = explosive, explosive, explosive); with a slow tempo of movement in the first repetition and an explosive tempo in the next two repetitions (S/E/E = slow, explosive, explosive); and with a slow tempo of movement in the first two repetitions and an explosive tempo in the last repetition (S/S/E = slow, slow, explosive). The slow repetitions were performed with a 5/0/5/0 (eccentric/isometric/concentric/isometric) movement tempo, while the explosive repetitions were performed with an X/0/X/0 (X- maximal speed of movement) movement tempo. During each experimental session, the participants performed one set of three repetitions at 60%1RM. The two-way repeated measures ANOVA showed a statistically significant interaction effect for peak power output (PP; p = 0.03; η 2 = 0.26) and for peak bar velocity (PV; p = 0.04; η 2 = 0.24). Futhermore there was a statistically significant main effect of condition for PP (p = 0.04; η 2 = 0.30) and PV (p = 0.02; η 2 = 0.35). The post hoc analysis for interaction revealed that PP was significantly higher in the 2nd and 3rd repetition for E/E/E compared with the S/S/E (p < 0.01 for both) and significantly higher in the 2nd repetition for the S/E/E compared with S/S/E (p < 0.01). The post hoc analysis for interaction revealed that PV was significantly higher in the 2nd and 3rd repetition for E/E/E compared with the S/S/E (p < 0.01 for both), and significantly higher in the 2nd repetition for the S/E/E compared with the S/S/E (p < 0.01). The post hoc analysis for main effect of condition revealed that PP and PV was significantly higher for the E/E/E compared to the S/S/E (p = 0.04; p = 0.02; respectively). The main finding of this study was that different distribution of movement tempo during a set has a significant impact on power output and bar velocity in the bench press exercise at 60%1RM. However, the use of one slow repetition at the beginning of a set does not decrease the level of power output in the third repetition of that set.

Novel tricyclic[2,1-f]theophylline derivatives of LCAP with activity in mouse models of affective disorders.

OBJECTIVES: The purpose of this study was to investigate the central activity of the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic 5HT1A receptor agonists and postsynaptic 5HT1A , 5HT2A and D2 receptors antagonists. The compounds were examined using animal tests towards antipsychotic, antidepressant- and anxiolytic-like properties and then compared with effects evoked by an atypical antipsychotic drug ziprasidone. METHODS: D-amphetamine-induced hyperactivity test was used to determine antipsychotic-like activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test were conducted to investigate antidepressant- and antianxiety-like activity, respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone were administered intraperitoneally 60 min before the tests. Diazepam and imipramine were used as standard anxiolytic and antidepressant drugs, respectively. KEY FINDINGS: The obtained results demonstrate that new synthesized compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties in behavioural tests in mice. CONCLUSIONS: The present preclinical results indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine-2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an antipsychotic drug with additional antidepressant and anxiolytic properties.