The International Journal of Neuropsychopharmacology

Brief Report

Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors

Yong Kee Choia1a2, Erik H. F. Wonga3, Brian Henrya4, Mohammed Shahida5 and Frank I. Tarazia1a2 c1

a1 Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA, USA

a2 Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA, USA

a3 CNS Discovery, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

a4 Schering-Plough, Translational Medicine Research Centre, Singapore

a5 Schering-Plough, Newhouse, Lanarkshire, UK


Adrenergic (α1 and α2) 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 α1-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 α2-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.

(Received May 13 2009)

(Reviewed June 19 2009)

(Revised August 14 2009)

(Accepted September 18 2009)

(Online publication October 19 2009)


c1 Address for correspondence: Dr F. I. Tarazi, Laboratory of Psychiatric Neuroscience, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. Tel.: 617-855-3176 Fax: 617-855-3479 Email: