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119 results on '"Shimoyama, Megumi"'

4. Protective effect of a mitochondria‐targeting peptide against paclitaxel‐induced peripheral neuropathy.

Author

Itoh, Kensaku, Shimoyama, Megumi, Schiller, Peter W., and Toyama, Satoshi

Subjects
*PERIPHERAL neuropathy, *PEPTIDES, *NERVE fibers, *ANTINEOPLASTIC agents, *CLINICAL deterioration, KERATINOCYTE differentiation
Abstract

Chemotherapy‐induced peripheral neuropathy (CIPN) is a major side effect of several anticancer agents including paclitaxel, a chemotherapeutic drug widely used in cancer treatment. CIPN deteriorates patients' quality of life and compromises cancer treatment. Dysfunction or injury of mitochondria has been suggested to be involved in the induction of this neuropathy. SS‐20 is a tetrapeptide that targets mitochondria and restores mitochondrial bioenergetics. This study was aimed to examine the protective effect of SS‐20 against paclitaxel‐induced peripheral neuropathy using a murine model. Repeated administration of paclitaxel to mice induced peripheral neuropathy as demonstrated by the presence of mechanical allodynia and the loss of intraepidermal nerve fibers in the hind paw. Concomitant administration of SS‐20 protected against the development of the neuropathy. Our results suggest that SS‐20 may be a drug candidate for the prevention of CIPN. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined by titration for the treatment of breakthrough pain in Japanese cancer patients: a multicenter, randomized, placebo-controlled, double-blind phase III trial

Author

Shimoyama, Naohito, primary, Gomyo, Ikuo, additional, Katakami, Nobuyuki, additional, Okada, Masakuni, additional, Yukitoshi, Nobuyuki, additional, Ohta, Eri, additional, and Shimoyama, Megumi, additional

Published
2014
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37. Superior Analgesic Effect of H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), a Multifunctional Opioid Peptide, Compared to Morphine in a Rat Model of Neuropathic Pain.

Author

Shimoyama, Megumi, Schiller, Peter W., Shimoyama, Naohito, Toyama, Satoshi, and Szeto, Hazel H.

Subjects
*ANALGESICS, *OPIOID peptides, *MORPHINE, *LABORATORY rats, *NEUROPATHY, *HYPERALGESIA
Abstract

H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA) is a synthetic tetrapeptide with extraordinary selectivity for the mu-opioid receptor and is an extremely potent analgesic. [Dmt1]DALDA is unusual in the way that the greater part of its analgesic potency appears to be produced by its actions in the spinal cord. Furthermore, [Dmt1]DALDA inhibits norepinephrine re-uptake and is a mitochondria-targeted antioxidant. Such characteristics may make [Dmt1]DALDA particularly effective against neuropathic pain. The present study was designed to compare the effects of [Dmt1]DALDA and morphine on thermal hyperalgesia in an experimental neuropathic pain model. Neuropathic pain was induced in rats by surgical ligation of the L5 spinal nerve, and thermal pain thresholds were assessed by latencies of paw withdrawal to radiant heat. The increase in paw withdrawal latency was greater after the administration of [Dmt1]DALDA than that of morphine in neuropathic rats at doses that were equianalgesic in naïve animals. We conclude that [Dmt1]DALDA is more effective than morphine against thermal hyperalgesia in this experimental model of neuropathic pain. [ABSTRACT FROM AUTHOR]

Published
2012
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43. Endogenous Endomorphin-2 Contributes to Spinal κ-Opioid Antinociception.

Author

Shimoyama, Megumi, Toyama, Satoshi, Tagaito, Yugo, and Shimoyama, Naohito

Subjects
*OPIOID receptors, *OPIOID peptides, *ANALGESICS, *LABORATORY mice, *DYNORPHINS, *ENKEPHALINS, *IMMUNE serums
Abstract

Background/Aims: Multiple opioid receptor (OR) types and endogenous opioid peptides exist in the spinal dorsal horn and there may be interactions among these receptor types that involve opioid peptides. In a previous study we observed that antinociceptive effects of the selective κ-opioid receptor (κOR) agonist, U50,488H, was attenuated in μ-opioid receptor (μOR) knockout mice as compared to wild-type mice when administered spinally. This suggests that an interaction between κORs and μORs exits in the spinal cord. The present study was aimed at investigating whether endogenous opioid peptides were involved in such interaction. Methods: We examined whether the presence of antibodies to endogenous opioid peptides, endomorphin-2, met-enkephalin and dynorphin A affected the antinociceptive effects of spinal U50,488H in rats. The tail-flick test was used to assess pain thresholds. Results: The increase in tail-flick latency after spinal U50,488H was attenuated when the rats were pretreated intrathecally with antiserum against endomorphin-2. Pretreatments with antisera against met-enkephalin and dynorphin A had no effect on U50,488H antinociception. The antisera alone did not affect pain threshold. Conclusion: The results suggest that endomorphin-2, an endogenous opioid peptide highly selective to the μOR, plays a role in antinociception induced by κOR activation in the spinal cord. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2012
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49. Differential respiratory effects of [Dmt1]DALDA and morphine in mice

Author

Shimoyama, Megumi, Kuwaki, Tomoyuki, Nakamura, Akira, Fukuda, Yasuichiro, Shimoyama, Naohito, Schiller, Peter W., and Szeto, Hazel H.

Subjects
*PAIN management, *ALKALOIDS, *ANESTHESIA, *HYPOXEMIA
Abstract

Abstract: H-Dmt-d-Arg-Phe-Lys-NH2 ([Dmt1]DALDA, dDAL), a highly selective mu-opioid peptide, produces potent analgesia without respiratory depression after intrathecal administration. Despite carrying 3+ net charge, dDAL is also a potent analgesic after systemic administration. We compared the respiratory effects of dDAL and morphine after subcutaneous administration in mice using whole body plethysmography. Analgesic doses of 3 and 10 times ED50 were examined. Both drugs dose-dependently decreased respiratory frequency and minute volume in room air. Tidal volume was increased by the lower dose of morphine, while it was decreased by the higher dose of dDAL. The decrease in minute volume by dDAL and morphine was completely reversed by naloxone. No difference in ventilatory response to CO2 was observed between dDAL and morphine at three times ED50. Ventilatory response to hypoxia was significantly diminished by dDAL compared to morphine and saline, and this effect of dDAL was naloxone-irreversible. Thus dDAL likely reduces the sensitivity of the peripheral chemoreflex loop through a non-opioid action. [Copyright &y& Elsevier]

Published
2005
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