Occupancy of alpha7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using 11CCHIBA-1001 in Healthy Human Subjects.
- Author:
Masatomo ISHIKAWA
1
;
Muneyuki SAKATA
;
Jun TOYOHARA
;
Keiichi ODA
;
Kenji ISHII
;
Jin WU
;
Taisuke YOSHIDA
;
Masaomi IYO
;
Kiichi ISHIWATA
;
Kenji HASHIMOTO
Author Information
1. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. hashimoto@faculty.chiba-u.jp
- Publication Type:Original Article
- Keywords:
alpha7-nicotinic acetylcholine receptor;
Positron-emission tomography;
Tropisetron;
Ondansetron;
[11C]CHIBA-1001
- MeSH:
Administration, Oral;
Alzheimer Disease;
Brain;
Electrons;
Humans;
Indoles;
Male;
Neuroimaging;
Ondansetron;
Positron-Emission Tomography;
Postoperative Nausea and Vomiting;
Receptors, Cholinergic;
Receptors, Nicotinic;
Schizophrenia
- From:Clinical Psychopharmacology and Neuroscience
2011;9(3):111-116
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: Agonists of alpha7-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 alpha7-nAChRs in the brain, only 4-[11C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([11C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT3) 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 alpha7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [11C]CHIBA-1001 and PET. METHODS: Two serial dynamic PET scans using [11C]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 [11C]CHIBA-1001 in the human brain. CONCLUSION: This study shows that tropisetron, but not ondansetron, could bind to alpha7-nAChRs in the human brain after a single oral administration. Therefore, [11C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of alpha7-nAChRs in the human brain.
