Effect of the new antiepileptic drug retigabine in a rodent model of mania.
Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were therefore (1) to confirm previous findings with lithium and lamotrigine, and (2) to evaluate the effect of the novel compound retigabine on AMPH+CDP-induced hyperactivity in rats. In all experiments, co-administration of AMPH and CDP induced a significant increase (191-295%) in locomotor activity. Lithium chloride (0.9 mg/kg) and lamotrigine (20 mg/kg), which are known to effectively stabilize mood in humans, both significantly decreased AMPH+CDP-induced locomotor activity without affecting basal locomotor activity. The results furthermore indicate that retigabine, like lithium and lamotrigine, significantly and dose-dependently attenuates the induced hyperactivity at a lowest effective dose of 1.0 mg/kg, whereas basal locomotor activity is reduced only at doses 4.0 mg/kg. In conclusion, retigabine was found to have an antimanic-like effect in the AMPH+CDP-induced hyperactivity model, suggesting a potential role for retigabine in the treatment of mania and possibly in the management of bipolar disorder.
Dencker
Ditte
D
Department of Psychopharmacology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
Dias
Rebecca
R
Pedersen
Mette Lund
ML
Husum
Henriette
H
D000661:Amphetamine; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal; D001714:Bipolar Disorder / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D002219:Carbamates / Q000097:blood / Q000627:therapeutic use*; D002707:Chlordiazepoxide; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000077213:Lamotrigine; D018021:Lithium Chloride / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010655:Phenylenediamines / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000627:therapeutic use
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; D014227:Triazines; C101866:ezogabine; D002707:Chlordiazepoxide; D000661:Amphetamine; D018021:Lithium Chloride; D000077213:Lamotrigine