Morihiro Fujimura
Toray Industries
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Featured researches published by Morihiro Fujimura.
Brain Research | 2004
Tomohiko Suzuki; Naoki Izumimoto; Yuko Takezawa; Morihiro Fujimura; Yuko Togashi; Hiroshi Nagase; Toshiaki Tanaka; Takashi Endoh
Repeated administration of micro-opioid receptor agonist, morphine induces tolerance not only to the antinociceptive effect but also to other pharmacological effects, resulting in shortened working duration and decreased efficacy. But less is known about kappa-opioid agonist-induced tolerance. The tolerance-development potency of kappa-opioid receptor agonists with a focus on TRK-820 was characterized. After five administrations of kappa-opioid receptor agonists, TRK-820 (0.1-0.8 mg/kg), U-50,488H (10-80 mg/kg) and ICI-199,441 (0.025-0.2 mg/kg) subcutaneously over 3 days, tolerance to the antinociceptive effects, assessed by an acetic acid-induced abdominal constriction test, developed in a repeated dose-dependent manner. The tolerance-development potency of TRK-820 was the least among these kappa-opioid receptor agonists. Similarly, TRK-820 and U-50,488H induced tolerance to their sedative effects as judged by a wheel-running test in mice. Greater tolerance was developed to the sedative effect than to the antinociceptive effect in both compounds. After repeated administration, the number of kappa-opioid receptors in the mouse brain was reduced by U-50,488H (80 mg/kg) but not by TRK-820 (0.4 mg/kg). There was no change of the affinity by the treatment with both compounds. These results demonstrated that the kappa-opioid receptor agonists developed tolerance both to the antinociceptive and the sedative effects, though the tolerance to the sedative effect developed more readily than tolerance to the antinociceptive effect. The difference in the potency for down-regulating the kappa-opioid receptors in the brain may account for the tolerance-development potency of the compounds.
Journal of Pharmacology and Experimental Therapeutics | 2014
Morihiro Fujimura; Naoki Izumimoto; Shinobu Momen; Satoru Yoshikawa; Ryosuke Kobayashi; Sayoko Kanie; Mikito Hirakata; Toshikazu Komagata; Satoshi Okanishi; Tadatoshi Hashimoto; Naoki Yoshimura; Koji Kawai
We characterized TRK-130 (N-[(5R,6R,14S)-17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-yl]phthalimide; naltalimide), an opioid ligand, to clarify the therapeutic potential for overactive bladder (OAB). In radioligand-binding assays with cells expressing human µ-opioid receptors (MORs), δ-opioid receptors (DORs), or κ-opioid receptors (KORs), TRK-130 showed high selectivity for MORs (Ki for MORs, DORs, and KORs = 0.268, 121, and 8.97 nM, respectively). In a functional assay (cAMP accumulation) with cells expressing each human opioid receptor subtype, TRK-130 showed potent but partial agonistic activity for MORs [EC50 (Emax) for MORs, DORs, and KORs = 2.39 nM (66.1%), 26.1 nM (71.0%), and 9.51 nM (62.6%), respectively]. In isovolumetric rhythmic bladder contractions (RBCs) in anesthetized guinea pigs, TRK-130 dose-dependently prolonged the shutdown time (the duration of complete cessation of the bladder contractions) (ED30 = 0.0034 mg/kg i.v.) without affecting amplitude of RBCs. Furthermore, TRK-130 ameliorated formalin-induced frequent urination at doses of higher than 0.01 mg/kg p.o. in guinea pigs under the freely moving condition. Meanwhile, TRK-130 showed only a negligible effect on the gastrointestinal transit at doses of up to 10 mg/kg s.c. in mice. These results indicate that TRK-130 is a potent and selective human MOR partial agonist without undesirable opioid adverse effects such as constipation and enhances the storage function by suppressing the afferent limb of the micturition reflex pathway, suggesting that TRK-130 would be a new therapeutic agent for OAB.
Archive | 2003
Naoki Izumimoto; Koji Kawai; Kuniaki Kawamura; Morihiro Fujimura; Toshikazu Komagata
Archive | 2002
Toshiaki Tanaka; Kuniaki Kawamura; Morihiro Fujimura; Toshikazu Komagata; Jun Miyakawa; Ko Hasebe
Archive | 2000
Toshiaki Tanaka; Hiroshi Nagase; Takashi Endoh; Kuniaki Kawamura; Morihiro Fujimura; Toshikazu Komagata
Archive | 2006
Koji Kawai; Morihiro Fujimura; Sayoko Kanie; Yohei Noro
Archive | 2003
Naoki Izumimoto; Koji Kawai; Kuniaki Kawamura; Morihiro Fujimura; Toshikazu Komagata
International Urology and Nephrology | 2017
Morihiro Fujimura; Naoki Izumimoto; Sayoko Kanie; Ryosuke Kobayashi; Satoru Yoshikawa; Shinobu Momen; Mikito Hirakata; Toshikazu Komagata; Satoshi Okanishi; Masashi Iwata; Tadatoshi Hashimoto; Takayuki Doi; Naoki Yoshimura; Koji Kawai
Neurourology and Urodynamics | 2011
Koji Kawai; Morihiro Fujimura; Sayoko Kanie; Shinobu Momen; Naoki Izumimoto; Masashi Iwata; Satoshi Okanishi; Tadatoshi Hashimoto; Yasuyuki Awasaki; Nobuyuki Nishida; Mikio Sasaki; Tomoji Yanagita
Archive | 2007
Morihiro Fujimura; Naoki Izumimoto; Koji Kawai; Kuniaki Kawamura; Toshikazu Komagata; 邦昭 川村; 孝治 河合; 直樹 泉本; 森広 藤村; 俊和 駒形