Electrophysiological characterization of the effects of asenapine at 5-HT(1A), 5-HT(2A), alpha(2)-adrenergic and D(2) receptors in the rat brain

Eur Neuropsychopharmacol. 2009 Mar;19(3):177-87. doi: 10.1016/j.euroneuro.2008.11.001. Epub 2008 Dec 29.


Asenapine is a psychopharmacologic agent being developed for schizophrenia and bipolar disorder. This study electrophysiologically characterized the in vivo effects of asenapine at dorsal raphe nucleus (DRN) and hippocampus serotonin-1A (5-HT(1A)), ventral tegmental area D(2), locus coeruleus 5-HT(2A,) and alpha(2)-adrenergic receptors in anesthetized rats. Asenapine displayed potent antagonistic activity at alpha(2)-adrenoceptors (ED(50), 85+/-2 microg/kg), 5-HT(2A) (ED(50), 75+/-2 microg/kg) and D(2) receptors (ED(50), 40+/-2 microg/kg) as evidenced by its reversal of clonidine-, DOI-, and apomorphine-induced inhibition of norepinephrine and dopamine neurons. In contrast, asenapine acted as a partial agonist at 5-HT(1A) receptors in DRN and hippocampus, as indicated by blockade of its inhibitory effect on neuronal firing by the 5-HT(1A) antagonist WAY 100635 and the partial inhibition of the suppressant action of 5-HT when co-applied by microiontophoresis. These results confirm that asenapine displays potent antagonistic activity at 5-HT(2A), D(2), alpha(2)-adrenergic receptors and provide evidence to support its 5-HT(1A) partial agonistic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Action Potentials / drug effects
  • Adrenergic alpha-2 Receptor Agonists
  • Amphetamines / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Brain / cytology*
  • Clonidine / pharmacology
  • Dibenzocycloheptenes
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Receptor, Serotonin, 5-HT2A / physiology*
  • Receptors, Adrenergic, alpha-2 / physiology*
  • Receptors, Dopamine D2 / agonists
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT2 Receptor Agonists


  • Adra2a protein, rat
  • Adrenergic alpha-2 Receptor Agonists
  • Amphetamines
  • Dibenzocycloheptenes
  • Heterocyclic Compounds, 4 or More Rings
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-2
  • Receptors, Dopamine D2
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT2 Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • asenapine
  • Clonidine
  • Apomorphine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine