So DCS was only taken twice: prior to each of the two sessions that were separated by average of 12 days. Similar to the rats in the preclinical work, participants receiving DCS exhibited significantly more improvement than did participants receiving placebo, measured either 1 week or 3 months later, long after the drug was out of the body (Figure 1A).74 At the 1-week follow-up, DCS-treated patients exhibited less subjective fear and fewer skin conductance fluctuations in the virtual reality environment. Figure 1A. Figure 1. Facilitation of exposure-based psychotherapy by D-cycloserine (DCS) in patients with fear of heights Inhibitors,research,lifescience,medical (A); social phobia (B); obsessive-compulsive

disorder (C), or panic disorder (D). Most importantly, outside of the virtual reality environment patients reported a decrease in overall acrophobia Inhibitors,research,lifescience,medical symptoms, increased self-reports of TGX-221 clinical trial exposure to heights in the “real world,” and higher self-ratings of improvement. These later results are very important because they indicate that Inhibitors,research,lifescience,medical extinction of fear is not always context-specific, as seen so often in animal studies. The reason for this appears to be that humans begin to feel safe in

situations they previously avoided, once they have some successful psychotherapy and avoid these situations less often. People with fear of elevators do not want to continue to walk up 20 flights of stairs once they learn the elevator will not harm them. In contrast, rats have no opportunity to continue to extinguish because they are put back in their home cage with no further exposure to the fearful conditioned stimulus. So, the several measures of relapse from extinction may be overestimated in rodent studies. Other groups found that DCS enhanced exposure Inhibitors,research,lifescience,medical therapy for social anxiety disorder—Figure 1B,76,77 obsessivecompulsive disorder—Figure 1C,78,79 and panic disorder—Figure Inhibitors,research,lifescience,medical 1D,80 indicating that the DCS effect is a relatively general one. The failure of another study to see on effect in OCT)81 may have resulted from giving

DCS 4 hours prior to exposure therapy, which may have been too early. There has been one report of a failure of DCS to facilitate exposure therapy for subclinical spider phobia,82 and failures of DCS to facilitate extinction of Pavlovian conditioned fear in a laboratory situation in humans.73,82 Tolmetin However, these negative effects may indicate that DCS is useful only in people with clinically significant, maladaptive fear—consistent, perhaps, with the preclinical data suggesting that DCS is particularly effective in stressed animals (described above). A note of caution DCS may not work on re-extinction It should be recalled that NMDA antagonists block extinction the first time extinction training is carried out but not when rats are retrained and then extinguished again.50 The same is true for D-cycloserine.