Reference

Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures

Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Arroyo, Santiago; Anhut, Henning; Kugler, Alan R.; Lee, Caroline M.; Knapp, Lloyd E.; Garofalo, Elizabeth A.; Messmer, Silke (Pregabalin 1008-011 International Study Group; Department of Neurology, Medical College of Wisconsin, Froedtert Hospital, Milwaukee, WI 53226, USA). Epilepsia, 45(1), 20-27 (English) 2004 Blackwell Publishing, Inc. CODEN: EPILAK. ISSN: 0013-9580. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Purpose: To evaluate pregabalin (PGB), 150 mg/day, and PGB, 600 mg/day, as an add-on treatment for patients with refractory partial seizures concurrently treated with one to three anticonvulsants (AEDs). Methods: An international (13 countries), multicenter (45 centers), 12-wk, double-blind, randomized study in which patients with partial seizures received placebo (n = 96); PGB, 150 mg/day (n = 99); or PGB, 600 mg/day (n = 92); given 3 times a day (t.i.d.). The primary efficacy criterion was redn. in seizure frequency during treatment as compared with baseline, as measured by RRatio, the sym. percentage change in seizure rates detd. from daily seizure diaries. The RRatio between the 8-wk baseline (pretreatment phase) and the 12-wk treatment period were compared between each of the PGB groups and the placebo group by using an anal. of variance anal. of the intent-to-treat population. Results: PGB, 150 mg/day and 600 mg/day, were both significantly more effective than placebo in reducing the RRatio [-11.5 (p = 0.0007) and -31.4 (p ￡ 0.0001), resp., vs. 0.9]. These RRatio values correspond to seizure-frequency redns. from baseline of -1.8, 20.6, and 47.8% for placebo, 150 mg/day, and 600 mg/day, resp. PGB efficacy was significantly dose related (p ￡ 0.0001). Secondary efficacy variables corroborated the findings of the primary anal. Significantly more patients were responders (350% redn. in seizure frequency) in the PGB, 600 mg/day (43.5%), group than in the placebo group (6.2%) (p ￡ 0.001). PGB was well tolerated. Dose-related, treatment-emergent adverse events (310%), mostly mild or moderate in intensity, were somnolence, dizziness, ataxia, diplopia, and wt.In this experiment, several chemicals are used like 148553-50-8 gain. The withdrawal rate due to adverse events was 10% of patients at 150 mg/day and 18.5% of patients at 600 mg/day, compared with 6.2% of patients receiving placebo. Conclusions: PGB, 150 mg/day and 600 mg/day, is highly effective and well-tolerated add-on therapy in patients with partial seizures. .

Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C

Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Fehrenbacher, Jill C.; Taylor, Charles P.; Vasko, Michael R. ( Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA). Pain, 105(1-2), 133-141 (English) 2003 Elsevier Science Ltd.Several reagents with their cas registry numbers 141436-78-4 and 148553-50-8 are used here. CODEN: PAINDB. ISSN: 0304-3959. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Gabapentin and pregabalin are amino acid derivs. of GABA that have anticonvulsant, analgesic, and anxiolytic-like properties in animal models. The mechanisms of these effects, however, are not well understood. To ascertain whether these drugs have effects on sensory neurons, the authors studied their actions on capsaicin-evoked release of the sensory neuropeptides, substance P and CGRP from rat spinal cord slices in vitro. Although release of immunoreactive peptides from non-inflamed animals was not altered by either drug, prior in vivo treatment by intraplantar injection of complete Freund's adjuvant enhanced release from spinal tissues in vitro, which was attenuated by gabapentin and pregabalin. These drugs also reduced release of immunoreactive neuropeptides in spinal tissues pretreated in vitro with the protein kinase C activator, phorbol 12,13-dibutyrate. The authors' results suggest that gabapentin and pregabalin modulate the release of sensory neuropeptides, but only under conditions corresponding to significant inflammation-induced sensitization of the spinal cord. .