Occupancy of α7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using [^(11)C]CHIBA-1001 in Healthy Human Subjects
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (42)
- Clarke PB, "The fall and rise of neuronal alpha-bungarotoxin binding proteins", Trends Pharmacol Sci, 13, pp.407~413 (1992)
- Berg DK, "Nicotinic alpha 7 receptors: synaptic options and downstream signaling in neurons", J Neurobiol, 53, pp.512~523 (2002)
- Paterson D, "nicotinic receptors in the human brain", Prog Neurobiol, 61, pp.75~111 (2000)
- Levin ED, "Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization", Psychopharmacology (Berl), 184, pp.523~539 (2006)
- Toyohara J, "α7 Nicotinic receptor agonists: potential therapeutic drugs for treatment of cognitive impairments in schizophrenia and Alzheimer's disease", Open Med Chem J, 4, pp.37~56 (2010)
- Wu J, "Brain imaging of nicotinic receptors in Alzheimer's disease", Int J Alzheimers Dis, 2010, pp.548913~ (2010)
- Ishikawa M, "α7 nicotinic acetylcholine receptor as a potential therapeutic target for schizophrenia", Curr Pharm Des, 17, pp.121~129 (2011)
- Hashimoto K, "α7 Nicotinic receptor agonists as potential therapeutic drugs for schizophrenia", Curr Med Chem CNS Agents, 5, pp.171~184 (2005)
- Martin LF, "Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia", Psychopharmacology (Berl), 174, pp.54~64 (2004)
- Olincy A, "Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men", Biochem Pharmacol, 74, pp.1192~1201 (2007)
- Bertrand D, "Allosteric modulation of nicotinic acetylcholine receptors", Biochem Pharmacol, 74, pp.1155~1163 (2007)
- Faghih R, "Advances in the discovery of novel positive allosteric modulators of the alpha7 nicotinic acetylcholine receptor", Recent Pat CNS Drug Discov, 2, pp.99~106 (2007)
- Faghih R, "Allosteric modulators of the alpha7 nicotinic acetylcholine receptor", J Med Chem, 51, pp.701~712 (2008)
- Tietje KR, "Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties", CNS Neurosci Ther, 14, pp.65~82 (2008)
- Shimohama S, "Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models", Biol Pharm Bull, 32, pp.332~336 (2009)
- Heiss WD, "Brain receptor imaging", J Nucl Med, 47, pp.302~312 (2006)
- Horti AG, "The quest for Eldorado: development of radioligands for in vivo imaging of nicotinic acetylcholine receptors in human brain", Curr Pharm Des, 12, pp.3877~3900 (2006)
- Falk L, "Higher expression of alpha7 nicotinic acetylcholine receptors in human fetal compared to adult brain", Brain Res Dev Brain Res, 142, pp.151~160 (2003)
- Marutle A, "Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia", J Chem Neuroanat, 22, pp.115~126 (2001)
- Court J, "Nicotinic receptor abnormalities in Alzheimer's disease", Biol Psychiatry, 49, pp.175~184 (2001)
- James RW, "Characterization of iodinated derivatives of alpha-bungarotoxin", Hoppe Seylers Z Physiol Chem, 361, pp.1517~1524 (1980)
- methyllycaconitine: a new radioligand for labelling alpha 7-type neuronal nicotinic acetylcholine receptors, "Neuropharmacology", 1999, 679~690
- iodo-MLA). A new ligand for the alpha7 nicotinic acetylcholine receptor, "J Med Chem", 2000, 142~145
- Toyohara J, "Recent development of radioligands for imaging α7 nicotinic acetylcholine receptors in the brain", Curr Top Med Chem, 10, pp.1544~1557 (2010)
- CHIBA- 1001 for mapping alpha7 nicotinic receptors by positron emission tomography, "Ann Nucl Med", 2009, 301~309
- CHIBA-1001 in humans, "Nucl Med Biol", 2011, 443~448
- CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys, "PLoS One", 2008, e3231~
- Simpson K, "Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting", Drugs, 59, pp.1297~1315 (2000)
- Wilde MI, "A review of its pharmacology and preliminary clinical findings in novel applications", Drugs, 52, pp.773~794 (1996)
- Ye JH, "Ondansetron: a selective 5-HT3 receptor antagonist and its applications in CNSrelated disorders", CNS Drug Rev, 7, pp.199~213 (2001)
- Macor JE, "The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist", Bioorg Med Chem Lett, 11, pp.319~321 (2001)
- Papke RL, "Activity of alpha7- selective agonists at nicotinic and serotonin 5-HT3 receptors expressed in Xenopus oocytes", Bioorg Med Chem Lett, 14, pp.1849~1853 (2004)
- Nomiyama T, "Phase I study of tropisetron capsules in healthy volunteers. Single administration", Kiso to Rinsho, 29, pp.1523~1559 (1995)
- Kumagai Y, "Phase I study of ondansetron (the 2nd report) - Single intravenous dose study and continuous drip infusion dose study in healthy volunteers", Rinsyou-Iyaku, 8, pp.1495~1504 (1992)
- Fujiwara T, "Performance evaluation of a large axial fieldof- view PET scanner: SET-2400W", Ann Nucl Med, 11, pp.307~313 (1997)
- Logan J, "Distribution volume ratios without blood sampling from graphical analysis of PET data", J Cereb Blood Flow Metab, 16, pp.834~840 (1996)
- Varga J, "Modified regression model for the Logan plot", J Cereb Blood Flow Metab, 22, pp.240~244 (2002)
- CHIBA-1001 binding to alpha7 nicotinic acetylcholine receptors in the brain from rat, monkey, and human, "Brain Res", 2010, 200~208
- Hashimoto K, "Tropisetron improves deficient inhibitory auditory processing in DBA", 2 mice: role of alpha 7 nicotinic acetylcholine receptors, 2005, pp.183, 13~19
- Hashimoto K, "Phencyclidine- induced cognitive deficits in mice are improved by subsequent subchronic administration of tropisetron: role of alpha7 nicotinic receptors", Eur J Pharmacol, 553, pp.191~195 (2006)
- Koike K, "Tropisetron improves deficits in auditory P50 suppression in schizophrenia", Schizophr Res, 76, pp.67~72 (2005)
- Shiina A, "A randomised, double-blind, placebocontrolled trial of tropisetron in patients with schizophrenia", Ann Gen Psychiatry, 9, pp.27~ (2010)