Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors.
Adrenergic (alpha1 and alpha2) and cholinergic muscarinic (M1-M5) receptor binding in rat forebrain was quantified after 4 wk of twice-daily subcutaneous administration of asenapine or vehicle. Asenapine (0.03, 0.1, and 0.3 mg/kg) produced increases in [3H]prazosin binding to alpha1-adrenergic receptors in the medial prefrontal cortex (mPFC: 30%, 39%, 57%) and dorsolateral frontal cortex (DFC: 27%, 37%, 53%) and increased [3H]RX821002 binding to alpha2-adrenergic receptors in mPFC (36%, 43%, 50%) and DFC (41%, 44%, 52%). Despite showing no appreciable affinity for muscarinic receptors, asenapine produced regionally selective increases in binding of [3H]QNB to M1-M5 receptors in mPFC (26%, 31%, 43%), DFC (27%, 34%, 41%), and hippocampal CA1 (40%, 44%, 42%) and CA3 (25%, 52%, 48%) regions. These regionally selective effects of asenapine on adrenergic and cholinergic muscarinic receptor subtypes may contribute to its beneficial clinical effects in the treatment of schizophrenia and bipolar disorder.
Choi
Yong Kee
YK
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA.
Wong
Erik H F
EH
Henry
Brian
B
Shahid
Mohammed
M
Tarazi
Frank I
FI
D018663:Adrenergic Agents / Q000493:pharmacokinetics; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D018678:Cholinergic Agents / Q000493:pharmacokinetics; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D066298:In Vitro Techniques; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium / Q000378:metabolism
D018663:Adrenergic Agents; D014150:Antipsychotic Agents; D018678:Cholinergic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D014316:Tritium; C522667:asenapine