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- 저자 : Muneyuki Sakata (검색결과 1 건)
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Masatomo Ishikawa,Muneyuki Sakata,Jun Toyohara,Keiichi Oda,Kenji Ishii,Jin Wu,Taisuke Yoshida,Masaomi Iyo,Kiichi Ishiwata,갠지하시모토 대한정신약물학회 2011 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.9 No.3
Objective: Agonists of α7-nicotinic acetylcholine receptors (nAChRs) have been developed as potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia and Alzheimer’s disease. Positron emission tomography (PET) is a noninvasive brain imaging technique to measure receptor occupancy in the living human brain. Although much effort has been expended to create specific PET radioligands for α7-nAChRs in the brain, only 4-[^(11)C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([^(11)C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT_3)receptor antagonists, tropisetron and ondansetron, have been used to treat patients with chemotherapy-induced or postoperative nausea and vomiting. Furthermore, tropisetron, but not ondansetron, possesses high affinity for α7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [^(11)C]CHIBA-1001 and PET. Methods: Two serial dynamic PET scans using [^(11)C]CHIBA-1001 in healthy non-smoking male subjects were performed before and after receiving an oral administration of these medications. Results: A single oral administration of tropisetron, but not ondansetron, decreased the total distribution volume of [^(11)C]CHIBA-1001 in the human brain. Conclusion: This study shows that tropisetron, but not ondansetron, could bind to α7-nAChRs in the human brain after a single oral administration. Therefore, [^(11)C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of α7-nAChRs in the human brain.
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