| Description: |
Asenapine maleate is a 5-HT (1A, 1B, 2A, 2B, 2C, 5A, 6, 7) and D2 antagonist with Ki values of 0.03-4.0 nM, 1.3nM, respectively, and an antipsychotic. |
| Target: |
5-HT1A Receptor:2.5 nM (Ki)
5-HT2A Receptor:0.06 nM (Ki)
5-HT2C Receptor:0.03 nM (Ki)
5-HT7 Receptor:0.13 nM (Ki)
D2 Receptor:1.3 nM (Ki)
D3 Receptor:0.42 nM (Ki)
D4 Receptor:1.1 nM (Ki) |
| In Vivo: |
Asenapine is an atypical antipsychotic that is currently available for the treatment of schizophrenia and bipolar I disorder. Asenapine may have superior therapeutic effect on anxiety symptoms than other agents in rats[3]. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests in mice[4]. |
| In Vitro: |
Relative to its D2 receptor affinity, asenapine has a higher affinity for 5-HT2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT6, α2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaves as a potent antagonist (pKB) at 5-HT1A (7.4), 5-HT1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), α2A (7.3), α2B (8.3), α2C (6.8) and H1 (8.4) receptors[2]. |
| Animal Administration: |
Rats: Asenapine maleate is suspended in 10% hydroxypropyl-β-cyclodextrin and administered in a volume of 1 mL/kg body weight . Rats are individually fear conditioned using electrical foot shock in a Skinner box. Animals are injected intraperitoneally (i.p.) with asenapine, clozapine, olanzapine, buspirone, or SB242084 at 30 min before freezing behaviour assessment[3]. Mice: Male ICR mice are repeatedly treated with 0.1 or 0.3mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests[4]. |
| References: |
[1]. Stoner SC, et al. Asenapine: a clinical review of a second-generation antipsychotic. Clin Ther. 2012 May;34(5):1023-40.
[2]. Shahid M, et al. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73.
[3]. Ohyama M,et al. Asenapine reduces anxiety-related behaviours in rat conditioned fear stress model. Acta Neuropsychiatr. 2016 Dec;28(6):327-336.
[4]. Ene HM, et al. Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice. Acta Neuropsychiatr. 2016 Apr;28(2):85-91. |
