title: Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors.
abstract: 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.
authors.affiliation: Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Choi
authors.forename: Erik H F
authors.initials: EH
authors.lastname: Wong
authors.forename: Brian
authors.initials: B
authors.lastname: Henry
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shahid
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
mesh_terms: 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
chemical_list: 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