研究者詳細 - 杉本　幸雄

論文 - 杉本　幸雄

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Evaluation of the effects of anti-pruritic drugs on scratch responses using histamine H1 receptor-deficient mice. 国際誌

Yukio Sugimoto, Yosuke Nakamura, Maria Alejandra Hossen, Takeshi Watanabe, Chiaki Kamei

European journal of pharmacology 470 ( 1-2 ) 113 - 6 2003年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The effects of anti-pruritic drugs on scratching behavior associated with passive cutaneous anaphylaxis in histamine H(1) receptor-deficient and wild-type mice were studied. Passive sensitization with mouse monoclonal anti-dinitrophenyl-immunoglobulin E (IgE) resulted in an increase in the incidence of scratching behavior induced by intravenous injection of dinitrophenyl-ovalbumin in both wild-type and histamine H(1) receptor-deficient mice. The histamine H(1) receptor antagonist diphenhydramine inhibited scratching behavior induced by antigen in passively sensitized wild-type mice, whereas no effect was observed in histamine H(1) receptor-deficient mice. On the other hand, oxatomide inhibited scratching behavior in both mice, although the effect in wild-type mice was more potent than that in histamine H(1) receptor-deficient mice. Tranilast inhibited scratching behavior with the same potency in both mice. We concluded that the scratching behavior associated with passive cutaneous anaphylaxis involves not only histamine H(1) receptors but also other chemical mediators. Furthermore, the results of the present study indicated that oxatomide has an antagonistic effect on histamine H(1) receptors as well as anti-pruritic effect in vivo.

Inhibitory effects of propolis granular A P C on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. 国際誌

Yukio Sugimoto, Yoshinori Iba, Ryoji Kayasuga, Yasushi Kirino, Miyuki Nishiga, Maria Alejandra Hossen, Kiyoshi Okihara, Hiroyuki Sugimoto, Hideo Yamada, Chiaki Kamei

Cancer letters 193 ( 2 ) 155 - 9 2003年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

We examined the effect of propolis granular A. P. C on lung tumorigenesis in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6 days/week from 1 week before NNK administration and throughout the experiment. Sixteen weeks after the NNK treatment, the mice were killed and the number of surface lung tumors was measured. The number of lung tumors in mice treated with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that observed in control mice. Propolis granular A. P. C significantly decreased the number of lung tumors induced by NNK. These results indicate that propolis granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis in mice.

Possible role of mucosal mast cells in the recovery process of colitis induced by dextran sulfate sodium in rats

Yoshinori Iba, Yukio Sugimoto, Chiaki Kamei, Tohru Masukawa

International Immunopharmacology 3 ( 4 ) 485 - 491 2003年4月

掲載種別：研究論文（学術雑誌）

To clarify the role of mucosal mast cells in the lesion sites of colitis induced by dextran sulfate sodium (DSS) in rats, we investigated the histological changes and alterations relevant to mucosal mast cells in the spontaneous recovery process of colitis. Oral administration of 4% DSS solution for 11 days resulted in surface epithelial loss, crypt loss and goblet cell depletion in the rectal mucosa. A marked infiltration of inflammatory cells into the mucosa, which was consistent with a significant increase in myeloperoxidase (MPO) activity, was observed. In addition, mucosal mast cell number and rat mast cell protease (RMCP) I and II levels in the rectum increased at day 0 after DSS treatment, and most of the mucosal mast cells were degranulated. After replacing 4% DSS solution with water, re-epithelialization and restoration of goblet cells were observed at day 5 and day 10, respectively, but crypt damage was hardly recovered even at day 20. The elevated myeloperoxidase activity was significantly decreased from day 5 after DSS treatment. The increased number of mucosal mast cells was further elevated up to about 1.5-fold at day 10 and day 20 after DSS treatment and little degranulation was observed. In the spontaneous recovery process, the increased rat mast cell protease II level in the rectum was maintained for 20 days, while the increased rat mast cell protease I level was gradually decreased and recovered to control level. These results suggest that proliferated mucosal mast cells remained for 20 days, although most of infiltrated inflammatory cells disappeared in spontaneous recovery process of colitis. It may therefore be presumed that proliferated mucosal mast cells play a role in spontaneous recovery process of the colitis induced by DSS. © 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(02)00299-0

Effects of [Arg⁸]-vasopressin on regional cerebral blood flow in spontaneously hypertensive rats

N. Azuma, Y. Sugimoto, M. Mio, K. Shinomiya, Chiaki Kamei

Methods and Findings in Experimental and Clinical Pharmacology 25 ( 3 ) 193 - 197 2003年4月

掲載種別：研究論文（学術雑誌）

The effects of [Arg8]-vasopressin (AVP) and related compounds on regional cerebral blood flow (rCBF) in the hippocampus were studied using conscious spontaneously hypertensive rats (SHR). rCBF in the hippocampus decreased gradually with age in proportion to an increase in mean blood pressure. Subcutaneous injection of AVP caused a dose-dependent increase in rCBF in the hippocampus. The effects of the metabolic fragments AVP4-9 and AVP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V2 antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V2 agonist, increased rCBF in the hippocampus. On the other hand, the AVP-induced increase in rCBF in the hippocampus was not antagonized by OPC-21268, a vasopressin V1 antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site. © 2003 Prous Science. All rights reserved.

DOI： 10.1358/mf.2003.25.3.769639

Inhibitory effects of propolis granular A. P. C on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice

Yukio Sugimoto, Yoshinori Iba, Ryoji Kayasuga, Yasushi Kirino, Miyuki Nishiga, Maria Alejandra Hossen, Kiyoshi Okihara, Hiroyuki Sugimoto, Hideo Yamada, Chiaki Kamei

Cancer Letters 193 ( 2 ) 155 - 159 2003年4月

掲載種別：研究論文（学術雑誌）

We examined the effect of propolis granular A. P. C on lung tumorigenesis in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6 days/week from 1 week before NNK administration and throughout the experiment. Sixteen weeks after the NNK treatment, the mice were killed and the number of surface lung tumors was measured. The number of lung tumors in mice treated with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that observed in control mice. Propolis granular A. P. C significantly decreased the number of lung tumors induced by NNK. These results indicate that propolis granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis in mice. © 2003 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3835(03)00016-8

Effects of NMDA antagonist MK-801 on radial maze performance in Zucker rats. 国際誌

Miyuki Nishiga, Yoko Fujii, Yukio Sugimoto, Masako Konishi, Chiaki Kamei

Brain research 950 ( 1-2 ) 127 - 9 2002年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

We examined the participation of the NMDA receptor in the histaminergic system using radial maze performance in Zucker rats. Although pyrilamine caused a significant effect on spatial memory deficit in lean rats, no significant spatial memory deficit was observed in obese rats. On the other hand, MK-801 caused significant spatial memory deficits in obese rats in comparison with lean rats. These results indicate that the histaminergic neuron is not closely related with the radial maze performance in obese rats. In addition, the potent effect of MK-801 observed in obese rats compared with lean rats may be responsible for the activation of NMDA receptors in obese rats.

Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H(1) receptors. 国際誌

Ryoji Kayasuga, Yukio Sugimoto, Takeshi Watanabe, Chiaki Kamei

European journal of pharmacology 449 ( 3 ) 287 - 91 2002年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H(1) receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H(1) receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H(1) receptor-deficient mice. Histamine H(1) receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H(1) receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H(1) receptors and thromboxane A(2) receptors were involved in the responses.

Effect of docosahexaenoic acid-fortified Chlorella vulgaris strain CK22 on the radial maze performance in aged mice

Yukio Sugimoto, Chiyomi Taga, Miyuki Nishiga, Madoka Fujiwara, Fumiko Konishi, Kuniaki Tanaka, Chiaki Kamei

Biological and Pharmaceutical Bulletin 25 ( 8 ) 1090 - 1092 2002年8月

掲載種別：研究論文（学術雑誌）

Effect of docosahexaenoic acid (DHA) [22:6(n-3)]-fortified Chlorella oil fraction on radial maze performance was studied in aged mice. Male ICR mice aged 9 months were fed a diet containing 2 g DHA-fortified Chlorella oil fraction/100 g diet or normal diet (Control group) for 2 months. Two months after the start of feeding, the mice were tested for learning ability related to 2 types of memory, reference memory and working memory, with the partially (4 of 8) baited eight-arm radial maze. Reference memory is a kind of information that should be retained until the next trial. Working memory is a kind of information that disappears in a short time. Entry into the unbaited arms and repeated entry into the visited arms were defined as reference memory errors and working memory errors, respectively. DHA-fortified Chlorella oil fraction administration to mice for 2 months resulted in a significant decrease in the number of working memory errors without affecting the number of reference memory errors. A significant increase in the DHA content in the brain was also observed. These results suggest that the intake of DHA-fortified Chlorella oil fraction effectively enhances working memory in maze performance.

DOI： 10.1248/bpb.25.1090

Histamine H1 receptors are involved in mouse nasal allergic responses: a demonstration with H1 receptor-deficient mice. 国際誌

Ryoji Kayasuga, Yukio Sugimoto, Takeshi Watanabe, Chiaki Kamei

International immunopharmacology 2 ( 6 ) 745 - 50 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The role of histamine H1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H1 receptor-deficient mice. The histamine H1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent-manner in wild-type mice, but no such increase was found in histamine H1 receptor-deficient mice. On the other hand, the histamine H2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H1 receptors play an important role in nasal allergy symptoms induced by histamine.

Effects of the NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats. 国際誌

Miyuki Nishiga, Yukio Sugimoto, Chiyomi Taga, Yoko Fujii, Chiaki Kamei

Life sciences 70 ( 18 ) 2199 - 208 2002年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-arm radial maze in rats. A significant decrease in histamine content in the hippocampus was observed after long-term feeding of rats with a histidine-deficient diet. At the same time, significant enhancement of the acquisition process in radial maze performance was also observed. Pyrilamine did not show a significant effect on radial maze performance in histidine-deficient rats. On the other hand, pyrilamine caused a significant spatial memory deficit in control rats. Scopolamine was effective in inhibiting spatial memory in both histidine-deficient and control rats. MK-801 caused spatial memory deficits more potently in histidine-deficient rats than in controls. Brain glycine contents showed a significant increase in the hippocampus in histidine-deficient rats. These results indicated that the spatial memory deficits induced by MK-801 in histidine-deficient rats are closely related to increased glycine levels and activation of NMDA receptors.

Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L.

Toshio Inoue, Yukio Sugimoto, Hideki Masuda, Chiaki Kamei

Biological & pharmaceutical bulletin 25 ( 2 ) 256 - 9 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Six flavonoid glycosides, eriocitrin (1), narirutin (2), hesperidin (3), luteolin-7-O-rutinoside (4), isorhoifolin (5), diosmin (6), rosmarinic acid (7) and 5,7-dihydroxycromone-7-O-rutinoside (8), were isolated from the aerial part of Mentha piperita L. Among these compounds, compound 4 showed a potent inhibitory effect on histamine release induced by compound 48/80 and antigen-antibody reaction. This compound was more effective than luteolin and luteolin-7-O-glucoside in inhibiting histamine release from rat peritoneal mast cells. Compound 4 also caused a dose-related inhibition of the antigen-induced nasal response and significant effects were observed at doses of 100 and 300 mg/kg. These results indicate that compound 4 may be clinically useful in alleviating the nasal symptoms of allergic rhinitis.

Participation of mast cells in colitis inflammation induced by dextran sulfate sodium

Y. Iba, Y. Sugimoto, C. Kamei

Methods and Findings in Experimental and Clinical Pharmacology 24 ( 1 ) 15 - 18 2002年

掲載種別：研究論文（学術雑誌）

We investigated the participation of mast cells in colitis inflammation induced by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO) activity were measured to confirm the occurrence of colitis. Rat mast cell protease (RMPCP) II levels in the serum were estimated as an index of mast cell degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), respectively. Administration of 4% DSS resulted in time-related increases in damage score, MPO activity and serum RMCP II levels, which were statistically significant at 7 and 11 days after treatment. Tissue RMCP I and RMCP II levels in the rectum were also increased significantly at 7 and 11 days, and 11 days, respectively after free drinking of 4% DSS. These results suggested that mast cells proliferated or the amount of protease per mast cell increased in the sites of inflammation induced by DSS, and that these mast cells may modulate the disorders observed in DSS-induced colitis. © 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.1.677122

Histamine H<inf>1</inf> receptors are involved in mouse nasal allergic responses: A demonstration with H<inf>1</inf> receptor-deficient mice

Ryoji Kayasuga, Yukio Sugimoto, Takeshi Watanabe, Chiaki Kamei

International Immunopharmacology 2 ( 6 ) 745 - 750 2002年

掲載種別：研究論文（学術雑誌）

The role of histamine H1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H1 receptor-deficient mice. The histamine H1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent manner in wild-type mice, but no such increase was found in histamine H1 receptor-deficient mice. On the other hand, the histamine H2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H1 receptors play an important role in nasal allergy symptoms induced by histamine. © 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1567-5769(02)00010-3

Changes in membrane potential induced by compound 48/80 in the peritoneal mast cells of rats

Y. Nakayama, M. Mio, Y. Sugimoto, Y. Fujii, Chiaki Kamei

Methods and Findings in Experimental and Clinical Pharmacology 24 ( 5 ) 267 - 273 2002年

掲載種別：研究論文（学術雑誌）

The changes in membrane potential induced by compound 48/80 were studied using rat peritoneal mast cells. The mean resting membrane potential of rat mast cells was -12.3 ± 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively. Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K+-pump, respectively. © 2002 Prous Science. All rights reserved.

DOI： 10.1358/mf.2002.24.5.802303

Effects of vasopressin on histamine H<inf>1</inf> receptor antagonist-induced spatial memory deficits in rats

Chiyomi Taga, Yukio Sugimoto, Miyuki Nishiga, Yoko Fujii, Chiaki Kamei

European Journal of Pharmacology 423 ( 2-3 ) 167 - 170 2001年7月

掲載種別：研究論文（学術雑誌）

The effects of [Arg8] vasopressin on histamine H1 receptor antagonist-induced memory deficits were investigated using the eight-arm radial maze performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increases in the number of total errors, reference memory errors and working memory errors. [Arg8] vasopressin improved not only scopolamine-but also pyrilamine-and diphenhydramine-induced memory deficits, although a high dose of [Arg8] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg8] vasopressin content were studied, and the hippocampus [Arg8] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg8] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory. © 2001 Elsevier Science B.V.

DOI： 10.1016/S0014-2999(01)01080-9

Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats

Toshio Inoue, Yukio Sugimoto, Hideki Masuda, Chiaki Kamei

Biological and Pharmaceutical Bulletin 24 ( 1 ) 92 - 95 2001年

掲載種別：研究論文（学術雑誌）

The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 μg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 μg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.

DOI： 10.1248/bpb.24.92

Effects of histidine on working memory deficits induced by the 5-HT<inf>1A</inf>-receptor agonist 8-OH-DPAT

S. Isayama, Y. Sugimoto, M. Nishiga, C. Kamei

Japanese Journal of Pharmacology 86 ( 4 ) 451 - 453 2001年

掲載種別：研究論文（学術雑誌）

We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Working memory deficits were elicited by 8-OH-DPAT without affecting reference memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at doses causing a significant increase in brain histamine content. This finding suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory deficit.

DOI： 10.1254/jjp.86.451

Involvement of mast cells in inflammation sites of colitis induced by dextran sulfate sodium 査読

Y Iba, Y Sugimoto, C Kamei

HISTAMINE RESEARCH IN THE NEW MILLENNIUM 1224 439 - 440 2001年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：ELSEVIER SCIENCE BV

We investigated the role of mast cells in the sites of inflammation in colitis induced by dextran sulfate sodium (DSS). Haematoxylin and eosin staining revealed a marked infiltration of inflammatory cells and oedematous changes in mucosa and submucosa after drinking of 4% DSS. And, toluidine blue staining also revealed that the number of mast cells was increased after free drinking of 4% DSS. These results suggest that mast cells may modulate the disorder of DSS-induced colitis.

The role of endogenous histamine in learning and memory in rats 査読

C Kamei, Y Sugimoto, Z Chen

HISTAMINE RESEARCH IN THE NEW MILLENNIUM 1224 461 - 462 2001年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：ELSEVIER SCIENCE BV

To clarify the role of endogenous histamine in learning and memory, the effects of a-fluoromethylhistidine (FMH) on active avoidance response and spatial cognition were investigated in rats. Both intraperitoneal (i.p.) and intracerebro-ventricular (i.c.v.) injection of FMH caused a significant prolongation of the response latency in active avoidance response. FMH also showed spatial memory deficits characterized by an increase in the number of total errors and a decrease in the number of initial correct response. There was high correlation between the memory deficit and a decrease in the brain histamine content.

Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats

Chiaki Kamei, Masaya Ohuchi, Yukio Sugimoto, Chihiro Okuma

Brain Research 887 ( 1 ) 183 - 186 2000年12月

掲載種別：研究論文（学術雑誌）

In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism. © 2000 Elsevier Science B.V.

DOI： 10.1016/S0006-8993(00)03041-9

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