Ann E. Corbin

Pregabalin for the treatment of postherpetic neuralgia A randomized, placebo-controlled trial

Objective: To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). Methods: The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. Results: Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with ≥30% and ≥50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. Conclusions: Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.

Reduced amide bond neurotensin 8-13 mimetics with potent in vivo activity

Abstract Appropriately substituted 8–9 (ΨCH2NH) isosteres of neurotensin (NT) 8–13 have been found which are active as NT agonists in vitro and in vivo. SAR studies suggest that preventing amide bond hydrolysis at the 8–9 and 11–12 positions of NT(8–13) mimetics is important for producing compounds with potent activity in vivo. Other simplified replacements for the Arg-Arg portion of NT(8–13) are reported.