Asenapine alters the activity of monoaminergic systems following its subacute and long-term administration: An in vivo electrophysiological characterization

Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study

“…Acute administration of brexpiprazole increased the firing activity of LC NE neurons ( Figure 3A ). This firing activity remained elevated after repeated administration ( Figure 3B ), similarly to of the effect of sustained asenapine, clozapine, quetiapine, and olanzapine administration ( Ramirez and Wang, 1986 ; Seager et al, 2005 ; Chernoloz et al, 2012 ; Oosterhof et al, 2015 ). Interestingly, 2- and 14-day aripiprazole administration did not alter the firing activity of LC neurons ( Chernoloz et al, 2009 ), demonstrating distinct effects of aripiprazole and brexpiprazole on the NE system.…”

“…In accordance with its acute behavioral and in vivo electrophysiological effects ( Maeda et al, 2014b ; Oosterhof et al, 2014 ), brexpiprazole administration for 2 and 14 days potently reduced the inhibitory effect of DOI, thus demonstrating antagonistic action on 5-HT 2A receptors ( Figure 3D , E , G ). Using the same methodology, antagonistic effects on 5-HT 2A receptors were previously demonstrated following sustained asenapine and quetiapine + norquetiapine administration ( Chernoloz et al, 2012 ; Oosterhof et al, 2015 ). Notably, the in vitro affinity for 5-HT 2A receptor of asenapine (Ki = 0.06nM; Shahid et al, 2009 ), brexpiprazole (Ki=0.47nM; Maeda et al, 2014b ), and quetiapine + norquetiapine (quetiapine Ki=101nM [ Kroeze et al, 2003 ]; norquetiapine Ki=58nM [ Jensen et al, 2008 ]) is reflected in their respective complete, partial ( Figure 3G ), and slight blockade of DOI in vivo ( Chernoloz et al, 2012 ; Oosterhof et al, 2015 ).…”

“…Of particular interest, asenapine partially blocked the inhibitory effect of apomorphine on DA neurons after 2 days of administration, similarly to the effect of 2-day brexpiprazole administration. However, 21-day asenapine administration sensitized D 2 autoreceptors ( Oosterhof et al, 2015 ). In contrast, the response of VTA DA neurons to apomorphine was indistinguishably dampened following 2- and 14-day brexpiprazole administration, demonstrating unaltered D 2 receptor sensitivity following these drug regimens ( Figure 2C -E).…”

“…Electrophysiological recordings were performed as described previously ( Oosterhof et al, 2015 ). Briefly, chloral hydrate-anesthetized animals were mounted in a stereotaxic apparatus; body temperature was maintained at 37°C utilizing a thermistor-controlled heating pad.…”

Enantioseparation and determination of asenapine in biological fluid micromatrices by HPLC with diode array detection

“…Asenapine (5‐chloro‐2,3,3a,12b‐tetrahydro‐2‐methyl‐1 H ‐dibenz(2,3‐6,7)oxepino(4,5‐c)pyrrole, SNP, Figure ) is one of the most recent antipsychotic drugs commercialised for the treatment of bipolar disorder and schizophrenia: it gained approval in both the USA and the European Union for the treatment of manic or mixed episodes of bipolar I disorder and also for schizophrenia in the USA [http://www.ema.europa.eu/ema/index.jsp?curl = pages/medicines/human/medicines/001177/human_med_001379.jsp&mid = WC0b01ac058001d124; http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/022117s000ltr.pdf]. In contrast to most traditional neuroleptics and atypical antipsychotics (which have a bicyclic or tricyclic structure), SNP is a tetracyclic molecule somewhat akin to the antidepressants mianserin and mirtazapine . SNP has a very broad affinity spectrum toward CNS receptors, binding with antagonistic activity to serotonin 5‐HT 2C , 5‐HT 2A , 5‐HT 7 , 5‐HT 2B and 5‐HT 6 receptors, as well as to adrenergic α 2B , dopamine D 3 , histamine H 1 and H 2 and dopamine D 2S and D 2L ones, albeit with lower affinity .…”