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Effect of JM-1232(-), a New Sedative on Central Respiratory Activity in Newborn Rats

  • Junya Kuribayashi
  • Shun-ichi Kuwana
  • Yuki Hosokawa
  • Eiki Hatori
  • Junzo Takeda
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)

Abstract

JM-1232(-), a newly manufactured isoindole derivative, shows sedative effect at a lower concentration compared with propofol. In the present study, we analyzed the response of the central respiratory activity to JM-1232(-). The brainstem-spinal cord of a newborn rat was isolated and was continuously superfused with oxygenated artificial cerebrospinal fluid (ACSF). Rhythmic inspiratory burst activity was recorded from C4 spinal ventral root using a glass suction electrode. We measured C4 burst rate and amplitude of integrated C4 activity. After obtaining a control recording, the preparation was superfused with ACSF containing JM-1232(-) at 10, 100 or 500 μM for 10 min. The application of both 10 and 100 μM JM-1232(-) did not decrease C4 burst rate significantly. However, 500 μM JM-1232(-) reduced C4 burst rate. On the contrary, C4 burst amplitude was not affected by the application of JM-1232(-) for 10 min at any concentrations. In conclusion, JM-1232(-) at a low concentration (but presumably higher than hypnotic dose), did not depress the central respiratory activity, whereas at a high concentration depression was seen.

Keywords

Respiratory Depression Ventral Root Artificial Cerebrospinal Fluid Anesthetic Dose Hypnotic Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was Supported by Japan Society for the Promotion of Science KAKENHI (18791106 to Dr. Kuribayashi and 19603015 to Dr. Kuwana), Tokyo, Japan

References

  1. Chiba, S., Nishiyama, T., and Yamada, Y. (2009) The antinociceptive effects and pharmacological properties of JM-1232(-): A novel isoindoline derivative. Anesth. Analg. 108, 1008–1014.CrossRefGoogle Scholar
  2. Eldridge, F.L. (1971) Relationship between phrenic nerve activity and ventilation. Am. J. Physiol. 221, 535–543.PubMedGoogle Scholar
  3. Kanamitsu, N., Osaki, T., Itsuji, Y., Yoshimura, M., Tsujimoto, H., and Soga, M. (2007) Novel water-soluble sedative-hypnotic agents: Isoindolin-1-one derivatives. Chem. Pharm. Bull. (Tokyo) 55, 1682–1688.CrossRefGoogle Scholar
  4. Kashiwagi, M., Okada, Y., Kuwana, S., Sakuraba, S., Ochiai, R., and Takeda, J. (2004) A neuronal mechanism of propofol-induced central respiratory depression in newborn rats. Anesth. Analg. 99, 49–55.CrossRefPubMedGoogle Scholar
  5. Kuwana, S., Okada, Y., and Natsui, T. (1998) Effects of extracellular calcium and magnesium on central respiratory control in the brainstem-spinal cord of neonatal rat. Brain Res. 786, 194–204.CrossRefPubMedGoogle Scholar
  6. Masamune, T., Sato, H., Okuyama, K., Imai, Y., Iwashita, H., Ishiyama, T., Oguchi, T., Sessler, D.I., and Matsukawa, T. (2009) The shivering threshold in rabbits with JM-1232(-), a new benzodiazepine receptor agonist. Anesth. Analg. 109, 96–100.CrossRefPubMedGoogle Scholar
  7. Murakoshi, T., Suzue, T., and Tamai, S. (1985) A pharmacological study on respiratory rhythm in the isolated brainstem-spinal cord preparation of the newborn rat. Br. J. Pharmacol. 86, 95–104.PubMedGoogle Scholar
  8. Nishiyama, T., Chiba, S., and Yamada, Y. (2008) Antinociceptive property of intrathecal and intraperitoneal administration of a novel water-soluble isoindolin-1-one derivative, JM 1232 (-) in rats. Eur. J. Pharmacol. 596, 56–61.CrossRefPubMedGoogle Scholar
  9. Shyr, M.H., Tsai, T.H., Tan, P.P., Chen, C.F., and Chan, S.H. (1995) Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat. Neurosci. Lett. 184, 212–215.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Junya Kuribayashi
    • 1
    • 2
    • 3
  • Shun-ichi Kuwana
    • 4
  • Yuki Hosokawa
    • 2
  • Eiki Hatori
    • 2
  • Junzo Takeda
    • 2
  1. 1.Department of Physiology and PediatricsUniversity of AlbertaEdmontonCanada
  2. 2.Department of AnesthesiologyKeio University School of MedicineTokyoJapan
  3. 3.Department of AnesthesiologyKitasato Institute HospitalTokyoJapan
  4. 4.Uekusa Gakuen UniversityTokyoJapan

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