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.
Administration, Oral ; Alzheimer Disease ; Brain ; Electrons ; Humans ; Indoles ; Male ; Neuroimaging ; Ondansetron ; Positron-Emission Tomography ; Postoperative Nausea and Vomiting ; Receptors, Cholinergic ; Receptors, Nicotinic ; Schizophrenia

Both aortic dissection and aortic aneurysm are complicated with disseminated intravascular coagulation (DIC) at the rate of four percent. DIC is said to be caused by the imbalance between coagulation and fibrinolysis and is classified into three types : suppressed fibrinolysis, balanced fibrinolysis, and enhanced fibrinolysis. Tranexamic acid has effects on suppressing the fibrinolytic system by inhibiting the mechanism by which plasmin decomposes fibrin. It is generally considered that the use of tranexamic acid for DIC is contraindicated. However, some reports show its effectiveness for non-infective chronic DIC. We illustrate two cases of DIC with enhanced fibrinolysis which are complicated with aortic dissection or aortic aneurysm that were successfully treated with tranexamic acid.