| The shivering threshold in rabbits with JM-1232(-), a new benzodiazepine receptor agonist. | |
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MedLine Citation:
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PMID: 19439682 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: JM-1232(-) is a novel isoindoline derivative which shows sedative and hypnotic activities through the benzodiazepine site of gamma-aminobutyric acid type A (GABAA) receptors. Typical doses of midazolam, another GABAA receptor agonist, slightly reduce the shivering threshold in humans. We thus determined the extent to which JM-1232(-) decreases the shivering threshold. METHODS: Eighteen rabbits, lightly anesthetized with isoflurane 0.2 minimum alveolar anesthetic concentration (MAC), were randomly assigned to infusions of 1) saline (control), 2) 0.01 mg x kg(-1) x min(-1) JM-1232(-), or 3) 0.1 mg x kg(-1) x min(-1) JM-1232(-). Body temperature was reduced at a rate of 2-3 degrees C/h by perfusing water at 10 degrees C though a U-shaped plastic tube positioned in the colon. Cooling continued until shivering was observed by an investigator blinded to treatment, or until core temperature reached 34 degrees C. Core temperatures were recorded from the distal esophagus, and core temperature at the onset of shivering defined the threshold. Data were analyzed by one-way analysis of variance with Student-Newman-Keuls tests. Results are presented as means +/- SD; P < 0.05 was considered statistically significant. RESULTS: The rabbits given a saline infusion shivered at 36.5 +/- 0.3 degrees C. Five of the six rabbits given JM-1232(-) at a rate of 0.01 mg x kg(-1) x min(-1) shivered at 35.7 +/- 0.8 degrees C, and one of these rabbits failed to shiver at 34.0 degrees C. None of the rabbits given JM-1232(-) at a rate of 0.1 mg x kg(-1) x min(-1) shivered before reaching the 34.0 degrees C cutoff temperature. CONCLUSION: A low dose of JM-1232(-) reduced the shivering threshold in rabbits approximately 0.8 degrees C which is similar to the effects in humans given premedication doses of midazolam. In contrast, a 10-fold larger dose reduced the threshold more than 2.5 degrees C. This is a substantial decrement and might facilitate induction of therapeutic hypothermia. |
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Authors:
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Taishi Masamune; Hiroaki Sato; Katsumi Okuyama; Yusuke Imai; Hironobu Iwashita; Tadahiko Ishiyama; Takeshi Oguchi; Daniel I Sessler; Takashi Matsukawa |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-13 |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 109 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-18 Completed Date: 2009-07-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 96-100 Citation Subset: AIM; IM |
Affiliation:
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Operating Theatre, Yamanashi University Hospital, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. ezn00202@nifty.ne.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Temperature / drug effects, physiology Dose-Response Relationship, Drug Hypothermia / chemically induced, physiopathology Isoindoles / administration & dosage, pharmacology* Male Piperazines / administration & dosage, pharmacology* Rabbits Random Allocation Receptors, GABA-A / agonists*, physiology Shivering / drug effects*, physiology |
| Chemical | |
Reg. No./Substance:
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0/3-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-2-phenyl-3,5,6,7-tetrahydrocyclopenta(f)isoindol-1(2H)-one; 0/Isoindoles; 0/Piperazines; 0/Receptors, GABA-A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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