• Minoru Narita, Akira Yamashita, Satoshi Imai, Naoko Kuzumaki, Motohiro Matoba, Tsutomu Suzuki, Kazuhiro Torigoe, Kae Nakahara, Mahardian Rahmadi, Kazumi Yoshizawa, Hiroshi Horiuchi, Shigeto Hirayama, Toshimasa Itoh, Kiyoshi Shakunaga, Mitsuaki Yamasaki, and Hiroshi Nagase.
• Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
• Anesthesiology. 2012 Jan 1;116(1):159-69.

BackgroundThe 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.MethodsA 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.ResultsOlanzapine 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.ConclusionThese 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.

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