- 著者
- Eun-Joo Shin Jae-Hyung Bach Sung Youl Lee Jeong Min Kim Jinhwa Lee Jau-Shyong Hong Toshitaka Nabeshima Hyoung-Chun Kim
- 出版者
- (公社)日本薬理学会
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- vol.116, no.2, pp.137-148, 2011 (Released:2011-06-16)
- 参考文献数
- 100
- 被引用文献数
- 11 28
Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.
- 著者
- Eun-Joo Shin Wan Kyunn Whang Sungun Kim Jae-Hyung Bach Jin-Man Kim Xuan-Khanh Thi Nguyen Thuy-Ty Lan Nguyen Bae Dong Jung Kiyofumi Yamada Toshitaka Nabeshima Hyoung-Chun Kim
- 出版者
- (公社)日本薬理学会
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- vol.113, no.4, pp.404-408, 2010 (Released:2010-08-18)
- 参考文献数
- 15
- 被引用文献数
- 11 25
Parishin C, a major component of Gastrodia elata BLUME (GE), was purified from GE. Because GE modulates the serotonergic system and the 5-HT1A receptor is an important therapeutic target of schizophrenia, we examined whether parishin C affects phencyclidine-induced abnormal behaviors in mice. Phencyclidine-induced abnormal behaviors were significantly ameliorated by parishin C. These effects were reversed by WAY 100635, a 5HT1A–receptor antagonist. Consistently, parishin C showed high affinity at 5-HT1A receptor as well as a 5-HT1A–agonist activity in a 8-OH-DPAT–stimulated [35S]GTP-γS binding assay. Our results suggest that the antipsychotic effects of parishin C require activation of 5-HT1A receptors.
- 著者
- Kiyofumi Yamada Toshitaka Nabeshima
- 出版者
- (公社)日本薬理学会
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- vol.91, no.4, pp.267-270, 2003 (Released:2003-04-21)
- 参考文献数
- 30
- 被引用文献数
- 177 447
Activity-dependent changes in synaptic strength are considered mechanisms underlying learning and memory. Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity such as long-term potentiation. Recent experimental evidence supports the role of BDNF in memory processes: Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor TrkB. Genetic as well as pharmacologic deprivation of BDNF or TrkB impairs learning and memory. In a positively motivated radial arm maze test, activation of the TrkB/phosphatidylinositol-3 kinase (PI3-K) signaling pathway in the hippocampus is associated with consolidation of spatial memory through an activation of translational processes. In a negatively motivated passive avoidance test, mitogen-activated protein kinase (MAPK) is activated during acquisition of fear memory. Furthermore, recent findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory. A Src-family tyrosine kinase, Fyn plays a role in this interaction by linking TrkB with NR2B. These findings suggest that BDNF/TrkB signaling in the hippocampus plays a crucial role in learning and memory.
- 著者
- Eun-Joo Shin Phil Ho Lee Hyun Ji Kim Toshitaka Nabeshima Hyoung-Chun Kim
- 出版者
- The Japanese Pharmacological Society
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- vol.106, no.1, pp.22-27, 2008 (Released:2008-01-22)
- 参考文献数
- 42
- 被引用文献数
- 15 16
Drug abuse involving dextromethorphan, an antitussive, has been a social problem in various geographic locations since the 1960s. Ironically, high doses of the drug confer neuroprotective activity with central nervous system and behavioral effects. Accumulating evidence suggests that metabolism to phencyclidine-like dextrorphan is not essential for the neuroprotective activity of dextromethorphan. Here, we review the neuroprotective properties of dextromethorphan and its potential for abuse and the potential neuroprotective effects of the drug’s analogs and 3-hydroxymorphinan, a metabolite of dextromethorphan. These compounds may provide a novel therapeutic direction for the treatment of neurodegenerative diseases such as convulsive or parkinsonian-like disorders.