Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin

Pharmacology, Biochemistry, and Behavior
Ayaka TataraYukihiro Ohno

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 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/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 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/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...Continue Reading

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Citations

Aug 11, 2016·Behavioural Brain Research·Naofumi KunisawaYukihiro Ohno
Oct 5, 2017·European Journal of Clinical Pharmacology·De-Wei ShangYu-Guan Wen
Feb 25, 2017·Frontiers in Pharmacology·Higor Alves IhaYukihiro Ohno
Feb 8, 2019·Neurotoxicity Research·Higor Alves IhaYukihiro Ohno

Related Concepts

Lonasen
AD 6048
Metazoa
Apokinon
Lenticulostriate Disorders
Behavior, Animal
Waxy Flexibility
Lentiform Nucleus Structure
Dose-Response Relationship, Drug
Haldol

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