title: Distinct electrophysiological effects of paliperidone and risperidone on the firing activity of rat serotonin and norepinephrine neurons.
abstract: BACKGROUND
  Paliperidone (9-OH-risperidone) is the main metabolite of the atypical antipsychotic risperidone. While both drugs are potent dopamine (D)2 antagonists, they have quantitative differential affinities for serotonin (5-HT) and norepinephrine (NE) receptor binding sites.
  
  
  OBJECTIVE
  The present study aimed to determine if paliperidone exerts distinct effects on 5-HT and NE neuronal activity from those of risperidone.
  
  
  METHODS
  Risperidone and paliperidone were administered to Sprague-Dawley rats. Neuronal activity of 5-HT and NE neurons was assessed using in vivo electrophysiology.
  
  
  RESULTS
  Acute administration of risperidone but not paliperidone inhibited the firing of 5-HT neurons, as previously reported. This inhibition was partially antagonized by the NE reuptake inhibitor desipramine, by the 5-HT(1A) receptor antagonist WAY 100635, and completely reversed when both drugs were given consecutively. Risperidone inhibited the firing of 5-HT neurons after 2 and 14 days of administration, with or without escitalopram. Paliperidone did not alter the firing rate of NE neurons by itself, but it reversed the suppression of NE neurons induced by escitalopram, as it was previously reported for risperidone.
  
  
  CONCLUSIONS
  These results indicate that although risperidone and paliperidone share a qualitatively similar receptor binding profile in vitro, they differentially alter the firing of 5-HT and NE neurons in vivo. The capacity of paliperidone to reverse the selective serotonin reuptake inhibitor (SSRI)-induced inhibition of NE neuronal firing, without interfering with the effect of SSRIs of 5-HT neuronal activity, suggests that paliperidone may be a very effective adjunct in SSRI-resistant depression.
authors.affiliation: University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue Suite 6419, Ottawa, ON K1Z-7K4, Canada. edremenc@rohcg.on.ca
authors.forename: Eliyahu
authors.initials: E
authors.lastname: Dremencov
authors.forename: Mostafa
authors.initials: M
authors.lastname: El Mansari
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007260:Infusion Pumps; D007275:Injections, Intravenous; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D000068882:Paliperidone Palmitate; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D014150:Antipsychotic Agents; D007555:Isoxazoles; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D015283:Citalopram; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D018967:Risperidone; D000068882:Paliperidone Palmitate; D003891:Desipramine; D009638:Norepinephrine