Asenapine-13C-D3 hydrochloride

Biological Activity

(±)-Asenapine-13C-d3 is intended for use as an internal standard for the quantification of (±)-asenapine by GC- or LC-MS. (±)-Asenapine is an atypical antipsychotic.1,2 It binds to dopamine D1-4, α-adrenergic, and histamine receptors (Kis = 0.42-1.45, 0.32-1.26, and 1-6.17 nM, respectively), as well as the serotonin (5-HT) receptor subtypes 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, and 5-HT7 (Kis = 0.03-3.98 nM).2 (±)-Asenapine inhibits the suppression of neuron firing induced by the 5-HT2A, dopamine D2, and α2-adrenergic receptor agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), apomorphine, and clonidine , respectively, in rat brain (ED50s = 75, 40, and 85 μg/kg, respectively).1 In vivo, (±)-asenapine (0.05-0.2 mg/kg, s.c.) increases extracellular dopamine levels in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral striatum and suppresses the conditioned avoidance response in rats.3 It prevents acute and chronic phencyclidine-induced deficits in cued reversal learning in rats when administered at a dose of 0.075 mg/kg.4 Formulations containing asenapine have been used in the treatment of schizophrenia and bipolar I disorder.

References

1.Ghanbari, R., El Mansari, M., Shahid, M., et al.Electrophysiological characterization of the effects of asenapine at 5-HT1A, 5-HT2A, α2-adrenergic and D2 receptors in the rat brainEur. Neuropsychopharmacol.19(3)177-187(2009) 2.Shahid, M., Walker, G.B., Zorn, S.H., et al.Asenapine: A novel psychopharmacologic agent with a unique human receptor signatureJ. Psychopharmacol.23(1)65-73(2009) 3.Fr?nberg, O., Wiker, C., Marcus, M.M., et al.Asenapine, a novel psychopharmacologic agent: Preclinical evidence for clinical effects in schizophreniaPsychoparmacol.(Berl).196(3)417-429(2008) 4.McLean, S.L., Neill, J.C., Idris, N.F., et al.Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the ratBehav. Brain Res.214(2)240-247(2010)