M. Tagawa; M. Kano; N. Okamura; M. Higuchi; M. Matsuda; Y. Mizuki; H. Arai; R. Iwata; T. Fujii; S. Komemushi; T. Ido; M. Itoh; H. Sasaki; T. Watanabe; K. Yanai. Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine.
British Journal of Clinical Pharmacology 52(5):501-509, 2001.
AIMS: Sedation induced by antihistamines is widely recognized to be caused by their penetration through the blood-brain-barrier and the consequent occupation of brain histamine H1-receptors. We previously studied the mechanism of sedation caused by antihistamines using positron emission tomography (PET). Recently, we revealed the nonsedative characteristic of ebastine, a second-generation antihistamine, with cognitive performance tests. In the present study, H1-receptor occupation by ebastine was examined in the human brain using PET. METHODS: Ebastine 10 mg and (+)-chlorpheniramine 2 or 6 mg were orally given to healthy male volunteers. PET scans with [11C]-doxepin, a potent H1-receptor antagonist, were conducted near tmax of respective drugs. Other volunteers in the control group also received PET scans. The binding potential of doxepin (BP = Bmax/Kd) for available brain H1-receptors was imaged on a voxel-by-voxel basis through graphical analysis. By setting regions of interest, the H1-receptor occupancy of drugs was calculated in several H1-receptor rich regions. RESULTS: Brain distribution of radioactivity after ebastine treatment was similar to that without any drugs. However, after the oral administration of 2 mg (+)-chlorpheniramine, the level was lower than after ebastine and nondrug treatments. Graphical analysis followed by statistical parametric mapping (SPM96) revealed that H1-receptor rich regions such as cortices, cingulate gyrus and thalamus were regions where the BPs after ebastine were significantly higher than after (+)-chlorpheniramine (2 mg). H1-receptor occupancies in cortex were approximately 10% by ebastine and > or = 50% by either dose of (+)-chlorpheniramine (95% confidence interval for difference in the mean receptor occupancies: 27%, 54% for 2 mg and 35%, 62% for 6 mg vs ebastine, respectively). Receptor occupancies increased with increasing plasma concentration of (+)-chlorpheniramine, but not with concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine (10 mg orally) causes brain histamine H1-receptor occupation of approximately 10%, consistent with its lower incidence of sedative effect, whereas (+)-chlorpheniramine occupied about 50% of brain H1-receptors even at a low but sedative dose of 2 mg; occupancy of (+)-chlorpheniramine was correlated with plasma (+)-chlorpheniramine concentration.Asymmetry: 0.00000 (left: -1, right: +1)
VRML2 file (65 Kb)
+1: 1.00000 M. Tagawa; M. Kano; N. Okamura; M. Higuchi; M. Matsuda; Y. Mizuki; H. Arai; R. Iwata; T. Fujii; S. Komemushi; T. Ido; M. Itoh; H. Sasaki; T. Watanabe; K. Yanai. Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine. British Journal of Clinical Pharmacology 52(5):501-509, 2001. PMID: 11736858. WOBIB: 127.
+2: 0.43078 Tatia M. C. Lee; Ho-Ling Liu; Li-Hai Tan; Chetwyn C. H. Chan; Srikanth Mahankali; Ching-Mei Feng; Jinwen Hou; Peter T. Fox; Jia-Hong Gao. Lie detection by functional magnetic resonance imaging. Human Brain Mapping 15(3):157-64, 2002. PMID: 11835606. WOBIB: 37.
+3: 0.40687 P. Maquet; J. Peters; J. Aerts; G. Delfiore; C. Degueldre; A. Luxen; G. Franck. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature 383(6596):163-6, 1996. PMID: 8774879. WOBIB: 96.
+4: 0.39100 R. J. Maddock; A. S. Garrett; Michael H. Buonocore. Remembering familiar people: the posterior cingulate cortex and autobiographical memory retrieval. Neuroscience 104(3):667-76, 2001. PMID: 11440800. WOBIB: 90.
+5: 0.39004 B. J. Casey; Jonathan D. Cohen; K. O'Craven; Richard J. Davidson; W. Irwin; C. A. Nelson; D. C. Noll; X. Hu; M. J. Lowe; B. R. Rosen; C. L. Truwitt; P. A. Turski. Reproducibility of fMRI results across four institutions using a spatial working memory task. NeuroImage 8(3):249-261, 1998. PMID: 9758739. FMRIDCID: . WOBIB: 116.
+6: 0.38008 Richard J. Maddock; Michael H. Buonocore. Activation of left posterior cingulate gyrus by the auditory presentation of threat-related words: an fMRI study. Psychiatry Research 75(1):1-14, 1997. PMID: 9287369. FMRIDCID: . WOBIB: 165.
+7: 0.36468 Brent A. Vogt; Stuart Derbyshire; Anthony K. Jones. Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. European Journal of Neuroscience 8(7):1461-73, 1996. PMID: 8758953. WOBIB: 100.
+8: 0.35813 Richard J. Maddock; Amy S. Garrett; Michael H. Buonocore. Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task. Human Brain Mapping 18(1):30-41, 2003. PMID: 12454910. DOI: 10.1002/hbm.10075. WOBIB: 39.
+9: 0.35130 Richard J. Maddock; Michael H. Buonocore; Shawn J. Kile; Amy S. Garrett. Brain regions showing increased activation by threat-related words in panic disorder. NeuroReport 14(3):325-328, 2003. PMID: 12634477. FMRIDCID: . WOBIB: 168.
+10: 0.33244 Gordon L. Shulman; Julie A. Fiez; Maurizio Corbetta; Randy L. Buckner; Francis M. Miezin; Marcus E. Raichle; Steven E. Petersen. Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex. Journal of Cognitive Neuroscience 9(5):648-663, 1997. FMRIDCID: . WOBIB: 173.
+11: 0.33103 Nicola M. Hunkin; Andrew R. Mayes; Lloyd J. Gregory; Amanda K. Nicholas; Julia A. Nunn; Michael J. Brammer; Edward T. Bullmore; Steven C. R. Williams. Novelty-related activation within the medial temporal lobes. Neuropsychologia 40(8):1456-1464, 2002. PMID: 11931949. FMRIDCID: . WOBIB: 143.
+12: 0.32468 K. L. Casey; T. J. Morrow; J. Lorenz; S. Minoshima. Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography. Journal of Neurophysiology 85(2):951-9, 2001. PMID: 11160525. WOBIB: 95.
+13: 0.32287 J. M. Ellermann; J. D. Siegal; J. P. Strupp; T. J. Ebner; K. Ugurbil. Activation of visuomotor systems during visually guided movements: a functional MRI study. Journal of Magnetic Resonance 131(2):272-285, 1998. PMID: 9571103. WOBIB: 45.
+14: 0.32128 P. Ruby; Jean Decety. Effect of subjective perspective taking during simulation of action: a PET investigation of agency. Nature Neuroscience 4(5):546-50, 2001. PMID: 11319565. DOI: 10.1038/87510. WOBIB: 8.
+15: 0.31840 K. B. McDermott; J. G. Ojemann; Steven E. Petersen; J. M. Ollinger; A. Z. Snyder; E. Akbudak; T. E. Conturo; Marcus E. Raichle. Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study. Memory 7(5-6):661-78, 1999. PMID: 10659091. WOBIB: 106.
+16: 0.31574 L. Ryan; L. Nadel; K. Keil; K. Putnam; D. Schnyer; T. Trouard; M. Moscovitch. Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people. Hippocampus 11(6):707-14, 2001. PMID: 11811665. WOBIB: 73.
+17: 0.31271 L. J. Adler; F. E. Gyulai; D. J. Diehl; M. A. Mintun; P. M. Winter; L. L. Firestone. Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography. Anesthesia & Analgesia 84(1):120-126, 1997. PMID: 8989012. WOBIB: 101.
+18: 0.31092 Gene E. Alexander; Kewei Chen; Pietro Pietrini; Stanley I. Rapoport; Eric M. Reiman. Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. American Journal of Psychiatry 159(5):738-45, 2002. PMID: 11986126. WOBIB: 91.
+19: 0.31083 C. Dettmers; R. N. Lemon; K. M. Stephan; G. R. Fink; Richard S. J. Frackowiak. Cerebral activation during the exertion of sustained static force in man. NeuroReport 7(13):2103-10, 1996. PMID: 8930968. WOBIB: 108.
+20: 0.30935 Takashi Tsukiura; Toshikatsu Fujii; Reiko Fukatsu; Taisuke Otsuki; Jiro Okuda; Atsushi Umetsu; Kyoko Suzuki; Michio Tabuchi; Isao Yanagawa; Tatsuo Nagasaka; Ryuta Kawashima; Hiroshi Fukuda; Shoki Takahashi; Atsushi Yamadori. Neural basis of the retrieval of people's names: evidence from brain-damaged patients and fMRI. Journal of Cognitive Neuroscience 14(6):922-37, 2002. PMID: 12191459. DOI: 10.1162/089892902760191144. FMRIDCID: 2-2002-112QC. WOBIB: 41.
+21: 0.30846 P. Pinel; S. Dehaene; D. Riviere; D. LeBihan. Modulation of parietal activation by semantic distance in a number comparison task. NeuroImage 14(5):1013-26, 2001. PMID: 11697933. DOI: 10.1006/nimg.2001.0913. WOBIB: 10.
+22: 0.30715 L. R. Becerra; H. C. Breiter; M. Stojanovic; S. Fishman; A. Edwards; A. R. Comite; R. G. Gonzalez; D. Borsook. Human brain activation under controlled thermal stimulation and habituation to noxious heat: an fMRI study. Magnetic Resonance in Medicine 41(5):1044-57, 1999. PMID: 10332889. WOBIB: 72.
+23: 0.29485 Paul C. Fletcher; F Happe; Uta Frith; S. C. Baker; Raymond J. Dolan; Richard S. J. Frackowiak; Chris D. Frith. Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension. Cognition 57(2):109-128, 1995. PMID: 8556839. DOI: 10.1016/0010-0277(95)00692-R. FMRIDCID: . WOBIB: 170.
+24: 0.29026 Kathryn M. Abel; Matthew P. G. Allin; Katarzyna Kucharska-Pietura; Anthony S. David; Chris Andrew; Steven C. R. Williams; Michael J. Brammer; Mary L. Phillips. Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study. NeuroReport 14(3):387-391, 2003. PMID: 12634489. DOI: 10.1097/01.wnr.0000058031.29600.31. FMRIDCID: . WOBIB: 155.
M. Fredrikson; G. Wik; Håkan Fischer; J. Andersson. Affective and attentive neural networks in humans: a PET study of
NeuroReport 7(1):97-101, 1995.
-1: 0.00023 Noam Sobel; V. Prabhakaran; John E. Desmond; Gary H. Glover; R. L. Goode; Edith V. Sullivan; John D. E. Gabrieli. Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature 392(6673):282-286, 1998. PMID: 9521322. DOI: 10.1038/32654. FMRIDCID: . WOBIB: 162.
-2: 0.00152 Dottie M. Clower; John M. Hoffman; John R. Votaw; Tracy L. Faber; Roger P. Woods; Garrett E. Alexander. Role of posterior parietal cortex in the recalibration of visually guided reaching. Nature 383(6601):618-21, 1996. PMID: 8857536. WOBIB: 109.
-3: 0.00153 Reginald B. J. Adams; Heather L. Gordon; Abigail A. Baird; Nalini Ambady; Robert E. Kleck. Effects of gaze on amygdala sensitivity to anger and fear faces. Science 300(5625):1536, 2003. PMID: 12791983. DOI: 10.1126/science.1082244. WOBIB: 86.
-4: 0.00157 Christian Gerlach; C. T. Aaside; G. W. Humphreys; Anders Gade; O. B. Paulson; I. Law. Brain activity related to integrative processes in visual object recognition: bottom-up integration and the modulatory influence of stored knowledge. Neuropsychologia 40(8):1254-67, 2002. PMID: 11931928. WOBIB: 7.
U. Hasson; T. Hendler; D. Ben Bashat; R. Malach. Vase or face? A neural correlate of shape-selective grouping processes in the human brain.
Journal of Cognitive Neuroscience 13(6):744-53, 2001.