title: Usefulness of olanzapine as an adjunct to opioid treatment and for the treatment of neuropathic pain.
abstract: BACKGROUND
  The use of opioids for pain management is often associated with nausea and vomiting. Although conventional antipsychotics are often used to counter emesis, they can be associated with extrapyramidal symptoms. However, chronic pain can induce sleep disturbance. The authors investigated the effects of the atypical antipsychotic olanzapine on morphine-induced emesis and the sleep dysregulation associated with chronic pain.
  
  
  METHODS
  A receptor binding assay was performed using mouse whole brain tissue. The emetic response in ferrets was evaluated by counting retching and vomiting behaviors. Catalepsy in mice was evaluated by placing both of their forepaws over a horizontal bar. Released dopamine was measured by an in vivo microdialysis study. Sleep disturbance in mice in a neuropathic pain-like state was assayed by electroencephalogram and electromyogram recordings.
  
  
  RESULTS
  Olanzapine showed high affinity for muscarinic M1 receptor in brain tissue. Olanzapine decreased morphine-induced nausea and vomiting in a dose-dependent manner. However, olanzapine at a dose that had an antiemetic effect (0.03 mg/kg) did not induce catalepsy or hyperglycemia. In addition, olanzapine at this dose had no effect on the morphine-induced release of dopamine or inhibition of gastrointestinal transit. Finally, olanzapine inhibited thermal hyperalgesia and completely alleviated the sleep disturbance induced by sciatic nerve ligation.
  
  
  CONCLUSIONS
  These findings suggest that olanzapine may be useful for the treatment of morphine-induced emesis and as an adjunct for the treatment of neuropathic pain associated with sleep disturbance.
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Kazuhiro
authors: K
authors: Torigoe
authors: Kae
authors: K
authors: Nakahara
authors: Mahardian
authors: M
authors: Rahmadi
authors: Kazumi
authors: K
authors: Yoshizawa
authors: Hiroshi
authors: H
authors: Horiuchi
authors: Shigeto
authors: S
authors: Hirayama
authors: Satoshi
authors: S
authors: Imai
authors: Naoko
authors: N
authors: Kuzumaki
authors: Toshimasa
authors: T
authors: Itoh
authors: Akira
authors: A
authors: Yamashita
authors: Kiyoshi
authors: K
authors: Shakunaga
authors: Mitsuaki
authors: M
authors: Yamasaki
authors: Hiroshi
authors: H
authors: Nagase
authors: Motohiro
authors: M
authors: Matoba
authors: Tsutomu
authors: T
authors: Suzuki
authors: Minoru
authors: M
authors: Narita
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D003024:Clozapine / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D006930:Hyperalgesia / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy*; D000077152:Olanzapine; D059408:Pain Management; D011985:Receptors, Serotonin / Q000378:metabolism; D012585:Sciatica / Q000517:prevention & control; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000701:Analgesics, Opioid; D014150:Antipsychotic Agents; D001786:Blood Glucose; D011985:Receptors, Serotonin; D001569:Benzodiazepines; D009020:Morphine; D003024:Clozapine; D000077152:Olanzapine; D004298:Dopamine