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1. Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome

Author

Satoshi Tsuchiya, Akira Sasaki, Yu Nakamura, Seiichi Kawada, Yasunori Oka, Hideto Shinno, Yasushi Inami, Toshihiko Innami, Takashi Hineno, Tetsuro Sakamoto, Soichi Mizuno, Manabu Otsuki, and Jun Horiguchi

Subjects
Adult, Male, medicine.drug_class, Severity of Illness Index, Antioxidants, Clonazepam, Hypnotic, Pramipexole, Restless Legs Syndrome, mental disorders, medicine, Humans, Benzothiazoles, Prospective Studies, Restless legs syndrome, GABA Modulators, Biological Psychiatry, Aged, Aged, 80 and over, Pharmacology, Dose-Response Relationship, Drug, musculoskeletal, neural, and ocular physiology, Epworth Sleepiness Scale, Middle Aged, medicine.disease, Crossover study, Tolerability, Anesthesia, Female, medicine.symptom, Psychology, Somnolence, medicine.drug
Abstract

Background Dopamine agonists are accepted as the first-line medications for restless legs syndrome (RLS). In some Asian countries, clonazepam is one of the prevalent medications for RLS because of its effect on sleep disturbances. To date, there have not been any studies that examined equivalent doses of pramipexole and clonazepam. To evaluate equivalent doses of pramipexole and clonazepam in RLS, we investigated the efficacy and tolerability after conversion from clonazepam to pramipexole, and examined dose equivalence between the two prescriptions. Methods In a prospective, open-label, multicenter study, 26 RLS patients treated with clonazepam (mean age: 69.2 ± 11.0 years old) were enrolled and then rapidly switched to pramipexole using a conversion calculation of 4:1 for daily doses. Then the daily dose of pramipexole was up titrated or tapered by 0.125 mg/day at each subsequent examination. RLS symptoms and daytime somnolence were evaluated using the International RLS Study Group rating scale (IRLS), Clinical Global Impressions — Severity of illness (CGI-S) and the Epworth Sleepiness Scale (ESS), respectively. Results Conversion from clonazepam to pramipexole resulted in significant reductions of IRLS (16.3 ± 8.7 to 9.1 ± 6.3) and ESS (6.5 ± 4.2 to 4.4 ± 3.2). CGI scores demonstrated improvement after conversion. In 4 patients (15%), adverse events such as somnolence, sensation of oppression in the lower limbs, diarrhea, or nausea were present. Correlation analysis demonstrated a significant relationship between these daily doses. Spearman's correlation coefficient was 0.662. Our study, however, has some limitations since it is an open-label trial and includes only 26 patients. Further studies using a double-blind design or a crossover design are recommended. Conclusions Statistical analysis demonstrated a 4:1 conversion for clonazepam to pramipexole. When switchover from clonazepam to pramipexole is done, this conversion ratio may be helpful to determine the initial dose of pramipexole for treating RLS.

Published
2010

2. Abstracts for the 6th Congress of Asian Sleep Research Society

Author

Xianchen Liu, Claudio L. Bassetti, Mia Son, Chen-Liang Lin, Yuichi Inoue, Zai-Ting Yeh, Kenji Suzuki, Ki-Young Jung, Emmanuel Mignot, Seung Hoon Lee, Hyun-Bo Sim, Sunao Uchida, Rayleigh Ping-Ying Chiang, Masayuki Miyamoto, Hiromi Mitsubayashi, Kazushige Goto, Aroonwan Preutthipan, Masato Kobayashi, Keiichi Sasaki, Yasunori Oka, Kwang-Jin Kim, Kaori Kinouchi, Seiichi Nakata, Satoru Tsuiki, Sachiko Horita, Ignatius Mark, Dae Han Chung, Joo Hwa Lee, Meng-Chen Tsou, Shinji Maritani, Toru Ogawa, Wenyu Ye, Birendra Nath Mallick, Yugo Ueda, Sung Pil Lee, Hsin Ju Chiang, Kazuyoshi Kitaoka, Tetsuro Sakamoto, Colin E. Sullivan, Takenao Sugi, Asami Suzuki, Nobuko Kajiwara, Lianqi Liu, Mikko Harma, Matthew T. Naughton, H. N. Mallick, Mikako Ohno, Susumu Hijuchi, Tae Kim, Chung Tai Lee, Ravindra P. Nagendra, Koki Sawada, Hae-Ran Na, Chiaki Tojo, Mitsuyuki Nakao, K. Kouno, Noriko Matsuura, Toshihiro Wakita, Kensuke Sumi, Toshiyuki Ojima, Ning-Hung Chen, Ryuichiro Yamamoto, Ryo Uchida, Chul Hee Lee, Jongbae Choi, Rei Ono, Jong Hyeon Jeong, Shintaro Chiba, Sachiko Chikahisa, Susumu Takahashi, Joong Saeng Cho, Ling Ling Tsai, M. Nirmala, M. Nakamori, Mituo Hayashi, H. Itoi, Takao Ayuse, Bonne Lee, Hong-Beom Shin, Bin Zhang, Yasunari Oka, Yoshiko Honda, Hirohiko Kanai, Minoru Onozuka, Emi Yamano, Eun Joong Kim, Kuniaki Tsuchiya, Bolortuya Yunren, Mahesh K. Kaushik, Paul B. Fitzgerald, Tomokazu Furukawa, Akira Matsuo, Ling-Ling Tsai, Lichao Chen, Toru Nakajima, Isa Okajima, Hsiao-Sui Lo, Shiori Matsuda, Michikazu Matsuda, Hideyo Tsutsui, Hidehisa Yamashita, Hyeon Kuk Lim, P. N. Ravindra, Kazufumi Yoshihara, Katsuo Yamazaki, Jiae Choi, Youngsoo Kim, Akemi Tomoda, Yasuyoshi Watanabe, Kazuo Yoshizaki, Min Jee Sung, Masato Saito, Hiroshi Hirai, Hiroshi Kadotani, Amornpong Vachiramon, Makoto Satoh, Deepak Shrivastava, Markus Dworak, Makoto Uchiyama, Mari Tazoe, Shinobu Sugihara, Takakazu Ishimatsu, Hiroyuki Sakai, Kazuhiro Sakai, Pradhan Nityanadan, Atsushi Yoshimura, Sang Doe Yi, Hyun Keuk Cha, Tatsuru Horikoshi, Jeong S. Kwon, Hyung Jun Ahn, Satomi Takahashi, Isao Hasegawa, Tomoko Fukuyama, Yukiyo Nakayama-Ashida, Gih Sung Chung, A. Murakami, Masako Okawa, Kazumi Takahashi, Yasushi Inami, Wael A. Ahmed, Tomoko Yoshikawa, Chia Chi Chen, H. Tanaka, Keitaro Yamashiro, Sachiko Suwa, Takuro Yamamoto, Anna V. Kalinchuk, Ying He, Jong Won Kim, Tatsuya Ishii, Yasuo Hishikawa, Shunji Moromugi, R. Ikeda, Itunari Minami, Takaya Nakamura, Sang Hag Lee, Shouhei Komori, Yang Wang, Tadashi Tanbara, Li-Ang Lee, Chia-Mo Lin, Hiroto Moriwaki, Kunio Kitahama, Velayudhan Mohan Kumar, Nigel McArdle, Yoshitaka Kaneita, Kenji Iwasaki, Hwa Ra Cho, Kenji Hirayama, Yoneatsu Osaki, Michael W. L. Chee, Nobuyuki Ozawa, Mitsuyasu Hiroki, Jamie C. Lam, Yukiko Nakamura, Cheon-Sik Kim, Christopher R. Jones, Eun-Ho Kang, Taichi Sakamoto, Mariko Nakauma, Sang Hun Jung, Sang-Yong Cho, Kazuyuki Shinohara, Yong Won Cho, Sang-Ahm Lee, Masahiko Kato, Ryuta Terashima, R. Taneike, David S.C. Hui, Ji Ho Choi, Noto Yamada, Jun Tokunaga, Ken-ichi Honma, Tae Hoon Kim, Miho Sekiguchi, Rumiko Kato, Tetsuo Shimizu, Nobuo Someya, Takeshi Munezawa, Yosuke Kato, Takashi Kanabayashi, Judith A. Owens, Takashi Ohida, Teruhisa Miike, T. Taguchi, Storu Tsuiki, Takeshi Mitani, Hirohito Tsuboi, Miyuki Fukazawa, Eun Joo Jang, Kayoko Ando, Seung Chul Hong, Siu Ping Lam, Soichiro Miyazaki, Kwang Suk Park, Tasuku Suzuki, Nobuhiro Fujiki, Antonia Jakobson, Mark R. Opp, Mika Shimizu, C. R. Chandrashekar, Masayuki Hirai, Siu Ping Joyce Lam, Asao Ito, Chia Ying Weng, Patrick M. Fuller, Tadahiro Ohtsu, T. Hamada, Katsunori Ishida, Manabu Otsuki, Mituaki Yamamoto, In-Young Yoon, Shulan Hsieh, Kazue Okamoto-Mizuno, Masahiro Oura, Tomoko Wakamura, Yoshihiko Koga, Nobuyuki Sudo, M. Takase, Seung Bong Hong, G. S. Lavekar, Talen Kin Hang Wai, Akifumi Kishi, Myeonggul Yeom, Cheng-Ning Huang, Takashi Abe, Sato Honma, Tatsuo Oka, Eui-Joong Kim, Fang Han, Shinichiro Tanaka, Yuu Tanaka, Hiroyoshi Sei, Do-Un Jeong, Kumiko Oi, Kyoko Nishihara, Seong T. Kim, Ken-Ichi Takahashi, Masanori Ookubo, Takashi Kanemura, Hiroshi Yamadera, Seiji Nishino, Yoshimasa Koyama, Keiko Maeda, Ming-Chieh Tsai, Men-Tzung Lo, Haruhiko Soma, Yuji Uchiyama, Masako Tamaki, Takeshi Sasaki, Yoshiharu Kinugasa, Robert W. McCarley, Kun Hee Lee, Kyoo In Chung, Tomoaki Sato, Mikako Kato, Mari Hagihara, Miyo Nakade, Misa Takegami, Michael Alexius A. Sarte, Lalaine Gedal, Bindu M. Kutty, Kouichi Ohsaki, Hideyuki Kanda, Higoshige Chiba, Shihomi Sakurai, Chisato Konno, Sathiamma Sulekha, Hideki Tanaka, Jong-Min Woo, Duk Shin, Akiko Abe, Jun-Ichi Suzuki, Min-Ying Lee, Sathyaprabha T. Narasappa, Y. Satoki, Seung Hyun Yoon, Takashi Kanbayashi, T. Sakohara, Masaaki Tanaka, Koh Mizuno, Crover Ho, Jirou Hitomi, Peter Watson, Won Chul Shin, Mitsuo Sasaki, Sakae Takahashi, Masato Matsuura, Shunichi Fukuhara, Benjamin C. H. Kwan, Yong-Seo Koo, Junko Kawatani, Seung Youp Shin, Ying-Hui Fu, Y. Kita, Yen-Ling Huang, Akiyo Takashima, Noriyuki Shimizu, Ryuji Furihata, Akira Komori, Hayashi Mitsuo, Koichi Iwanaga, J. Kamiyama, Chien-Ming Yang, Yoon Kyung Shin, Bum-Hee Yu, Marco Zucconi, Francoise Joseph, Chen Lin, Jong H. Choi, Chiyoe Murata, Hiroaki Yoshiyama, Satoko Hashimoto, Satoshi Yamamura, Toshimi Ito, Deokwon Ko, Takako Joudoi, Etsuko Hayashi, A. Hayashi, Jung Eun Yoon, Ji Hye Choi, Sadao Sato, Koji Murashima, Chia-Suo Wu, Hiroyuki Suzuki, Kyoko Imai-Matsumura, Takeya MurakI, K. Nakayama, Xin Shirley Li, Soichi Mizuno, Hideto Shinno, Shin Yamazaki, H. Yoshimura, Sung Wan Kim, Akira Sasaki, Yoko Komada, Kohei Shioda, Masaya Takahashi, Basavaraj R. Tubaki, Masahiro Suzuki, Hideki Ohira, Shuichiro Shirakawa, Radhika Basheer, Manzhen Shen, Koji Otani, Masumi Minowa, Ji Hee You, Jun Horiguchi, Ho Jun Seo, Young Min Ahn, Takahiro Kitanaka, Tohru Kodama, S. Sugimori, Ryoji Aritomi, Yoichi Nishimura, Makoto Endo, Hiroshi Nakano, Ritchie E. Brown, Benjamin H. Natelson, Emi Koyama, Mina Kobayashi, Tsuguo Nishijima, Taiki Komatsu, Katsunori Kondo, Madoka Takahara, Zbigniew R. Struzik, Masayuki Ozaki, Robert E. Strecker, Noiihiro Katayama, Tetsuaki Arai, Seiichi Kawada, Jihui Zhang, Yuko Morita, Takashi Hineno, Makoto Honda, Kei Mizuno, Hruda Nanda Mallick, Masahito Ogawa, Shoichi Asaoka, Yutaka Honda, Deependra Kumar, Yukiko Akai, Chul Ho Jung, Ikeda Hiroki, Yusaku Nakashima, Shih-Pin Hsu, Liang-Wen Hang, Sanjay Dubé, Y. Sakai, Fumiharu Togo, Kazuo Chin, Yu Nakamura, Toshiharu Takahashi, Akira Usui, Masatoshi Nakamura, Maki Furutani, Taeko Sasai, Yu-Shu Huang, Yukihiko Ito, Tomohide Kubo, Akio Yasuda, Sanae Fukuda, Seog Ju Kim, Pierre-Hervé Luppi, Kana Tokuyama, David M. Mckenzie, Kiyotaka Yanagihara, Yu Tanaka, Clara Inoue, Mitsuo Hayashi, Satoshi Tsuchiya, Park Chan Soon, Chiaki Shigemasa, Kingman P. Strohl, Akihiro Karashima, Kazuya Yoshida, Tokusei Tanahashi, Yuichi Kato, Miyuki Takano, Bertil B. Fredholm, Toshihiko Innami, Mitsuhiro Ohtsu, Katuo Yamazaki, Shinichi Konno, Yoshiharu Yamamoto, Ichiro Hisatome, Genya Matsuoka, Madelaine M. Wohlreich, Yasuhiro Sasao, In Kyoon Lyoo, Chol Shin, D. Sudhakar, Jason P. Kirkness, T. N. Sathyaprabha, Yau Hong Goh, David R. Hillman, Yu Jin Lee, Tomomi Kawauchi, Chiharu Kubo, Keiko Ogawa, Haruhiko Akiyama, Osamu Igawa, Eun-Mi Lee, Tadao Hori, Russell Conduit, Masahiro Matsumoto, Jin-Seong Lee, Takayuki Nakai, David J. Kennaway, Robert Strecker, Wai Man Mandy Yu, Toshihiro Hamada, Hiroe Takahashi, Yasuaki Hayashino, Tomomasa Ochiai, Ayano Kuriki, Manvir Bhatia, Jeong Su Lee, Shigeru Sakurai, Hiroki Kurahashi, Yun Kwok Wing, Wen-Yen Huang, Yue Nakahara, Shiko Yamashita, Hirokazu Doi, and Hsueh-Yu Li

Subjects
Health psychology, medicine.medical_specialty, Neuropsychology and Physiological Psychology, Neurology, Physiology, Physiology (medical), medicine, Sleep research, Human physiology, Psychology, Psychiatry
Published
2009

3. Nocturnal myoclonus observed in a patient with neuroleptic-induced akathisia

Author

Keiji Kondo, Akira Sasaki, Ohichi Nishimatsu, Jun Horiguchi, Yasushi Inami, and Toshihiko Innami

Subjects
Adult, Myoclonus, Sleep Wake Disorders, congenital, hereditary, and neonatal diseases and abnormalities, Neuroleptic induced akathisia, Polysomnogram, Nocturnal, Akathisia, mental disorders, medicine, Humans, Dose-Response Relationship, Drug, Electromyography, General Neuroscience, Electroencephalography, General Medicine, Clonazepam, nervous system diseases, Psychiatry and Mental health, Neurology, Psychotic Disorders, Close relationship, Anesthesia, Drug Therapy, Combination, Female, Neurology (clinical), Sleep Stages, medicine.symptom, Psychology, medicine.drug, Akathisia, Drug-Induced, Antipsychotic Agents
Abstract

An all-night polysomnogram was twice recorded in a patient with neuroleptk-induced akathisia (NIA). The polysomnogram revealed nocturnal myoclonus. After disappearance of akathisia by the administration of clonazepam, we recorded the second polysomnogram. At the second examination, sleep efficacy increased and the total number of nocturnal myoclonus decreased remarkably. The mean inter-movement interval of nocturnal myoclonus prolonged. These findings suggest a close relationship between the mechmisms of neuroleptic-induced akathisia and nocturnal myoclonus.

Published
1992

4. In vitro carboxymethylation of myelin basic protein

Author

Yasuo Kakimoto, Toshihiko Innami, and Masaharu Miyake

Subjects
Male, Proteolipid protein 1, Period (gene), In Vitro Techniques, Substrate Specificity, Myelin, Testis, medicine, Animals, Protein Methyltransferases, Lung, chemistry.chemical_classification, biology, General Neuroscience, Myocardium, Substrate (chemistry), Citrullination, Brain, Myelin Basic Protein, Rats, Inbred Strains, General Medicine, Protein O-Methyltransferase, In vitro, Myelin basic protein, Rats, medicine.anatomical_structure, Enzyme, nervous system, chemistry, Biochemistry, biology.protein, Cattle, Electrophoresis, Polyacrylamide Gel
Abstract

Summary During a study to find natural substrate proteins of carboxymethylation, myelin basic protein was found to be a good substrate. The two protein carboxymethylases were purified partially using myelin basic protein as a substrate. These two enzymes may be identical with protein carboxymethylase I and II, which have been found to methylate γ-globulin. The Km of myelin basic protein (25 μM) was very small compared with other substrates. The activities of the two carboxymethylases were high in the rat brain in comparison to the other rat organs. The activity increased during the period of myelination in the rat brain. These findings suggest that carboxymethylation of myelin basic protein may play an important role in myelination.

Published
1986

5. Protein carboxyl methylation in synaptic membrane of rat brain: the possible presence of adenosine-bound S-adenosyl-L-homocysteine hydrolase in the membrane

Author

Masaharu Miyake and Toshihiko Innami

Subjects
Male, Hydrolases, Synaptic Membranes, Nerve Tissue Proteins, Biology, Biochemistry, Cellular and Molecular Neuroscience, chemistry.chemical_compound, S-adenosyl-L-homocysteine hydrolase, medicine, Animals, cardiovascular diseases, Neurotransmitter, chemistry.chemical_classification, Cerebral Cortex, Adenosylhomocysteinase, Rats, Inbred Strains, Methylation, Adenosine, Molecular biology, nervous system diseases, Rats, Kinetics, Enzyme, chemistry, Membrane protein, Microsome, medicine.drug, Subcellular Fractions, Synaptosomes
Abstract

The effects of some neurotransmitters, adenosine (Ad), and homocysteine (Hcys) on protein carboxyl methylation in synaptic plasma membranes from rat cerebral cortex were examined. Neither any of the neurotransmitters nor Ad had a detectable effect. Incubation of the membrane with DL-Hcys alone (5 × 10-5M), the combination of both Ad (5 × 10-5) and DL-Hcys (5 × 10-5), or S-adenosyl-L-homocysteine (SAH) (1 × 10-6) strongly decreased the methyl ester formation. The inhibitory effect of the combination of both compounds may be interpreted in terms of the increased SAH concentration due to the presence of SAH hydrolase in the membrane. The inhibitory effect of Hcys alone was blocked by preincubation with Ad deaminase or Neplanocin A, a potent inhibitor of SAH hydrolase, suggesting the presence of Ad-bound SAH hydrolase in the synaptic membrane. Ad-bound SAH hydrolase activity estimated by the inhibition of methylation in the presence of Hcys was located in the membrane fractions including synaptosomes, myelin, and microsomes (about 70%), but the SAH hydrolase activity estimated on the basis of the inhibitory effect of the combination of both Ad and Hcys was localized exclusively in the soluble fraction (about 90%). The distribution of the latter activity is coincident with that of SAH hydrolase reported to date. Incubation of the synaptic membrane with Hcys alone and with the combination of both Ad and Hcys markedly increased the SAH concentration. The stimulatory effect of Hcys alone was blocked by Ad deaminase.

Published
1987

6. A beta-citryl-L-glutamate-hydrolysing enzyme in rat testes

Author

Yasuo Kakimoto, Toshihiko Innami, and Masaharu Miyake

Subjects
Male, GTP', Cations, Divalent, Biophysics, Biology, Biochemistry, Amidohydrolases, Substrate Specificity, Glutamates, Testis, medicine, Animals, Nucleotide, Aminohydrolase, Molecular Biology, Egtazic Acid, Edetic Acid, chemistry.chemical_classification, Amidohydrolase, Glutamate receptor, Skeletal muscle, Rats, Inbred Strains, Rats, Glutamine, Kinetics, Enzyme, medicine.anatomical_structure, chemistry
Abstract

An enzyme responsible for the deacylation of β-citryl- L -glutamate to citrate and glutamate has been characterized in rat testis. The enzyme required manganese ion for full activity and was strongly inhibited by nucleotides such as ATP or GTP. The activity was localized in the particulate fractions. The enzyme favored N- formyl- L -glutamate > β- citryl- L -glutamate > β- citryl- L -glutamine in a decreasing order. The amidohydrolyase activity was highest in the testis and lung, a moderate activity was detected in heart, kidney and intestine, and low in brain, thymus, stomach, skeletal muscle, spleen and liver. These findings suggest that the amidohydrolase is different from any of amidohydrolases reported so far, amidohydrolase I (EC 3.5.1.14), II (EC 3.5.1.15), III, N-acetyl-lysine deacylase (EC 3.5.1.17) and N-acetyl-β-alanine deacetylase (EC 3.5.1.21), and various peptidases.

Published
1983

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