Occupancy of alpha7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using 11CCHIBA-1001 in Healthy Human Subjects
Clinical Psychopharmacology and Neuroscience
;
: 111-116, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-179045
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Esquizofrenia
/
Encéfalo
/
Administração Oral
/
Receptores Colinérgicos
/
Receptores Nicotínicos
/
Ondansetron
/
Náusea e Vômito Pós-Operatórios
/
Tomografia por Emissão de Pósitrons
/
Elétrons
/
Doença de Alzheimer
Limite:
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Clinical Psychopharmacology and Neuroscience
Ano de publicação:
2011
Tipo de documento:
Artigo
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