Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2012709 | Pharmacology Biochemistry and Behavior | 2015 | 6 Pages |
Abstract
Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1Â mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200Â mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10Â mg/kg, s.c.), whereas HAL at doses of 0.1-3Â mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Ayaka Tatara, Saki Shimizu, Atsushi Masui, Miyuki Tamura, Shoko Minamimoto, Yuto Mizuguchi, Midori Ochiai, Yusuke Mizobe, Yukihiro Ohno,