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JM-1232(-) and propofol, a new combination of hypnotics with short-acting and non-cumulative preferable properties.
Taharabaru, Saori; Tamura, Takahiro; Higashi, Michiko; Matsuda, Naoyuki; Satomoto, Maiko; Adachi, Yushi U; Sato, Aiji Boku; Okuda, Masahiro.
Afiliação
  • Taharabaru S; Department of Anesthesia, Nishio Municipal Hospital, Nishio Municipal Hospital, 6 Kamiawahara, Kumami-cho, Nishio, Aichi 4458510, Japan.
  • Tamura T; Department of Anesthesiology, Aichi Gakuin University School of Dentistry, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 4658651, Japan.
  • Higashi M; Department of Surgical Intensive Care Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 4668550, Japan.
  • Matsuda N; Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 4668550, Japan.
  • Satomoto M; Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 4668550, Japan.
  • Adachi YU; Department of Anesthesiology, Toho University School of Medicine, Toho University Medical Center, Ohmori Hospital, 6-11-1 Ohmori-Nishi, Ohta-ku, Tokyo 1438541, Japan.
  • Sato AB; Department of Anesthesia and Intensive Care Medicine, International University of Health and Welfare, 537-3 Iguchi, Nasushiobara, Tochigi 3292763, Japan.
  • Okuda M; Department of Anesthesiology, Aichi Gakuin University School of Dentistry, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 4658651, Japan.
Exp Anim ; 70(1): 101-107, 2021 Feb 06.
Article em En | MEDLINE | ID: mdl-33071272
Drug interactions are significant in anesthesiology because drug combinations can potentially possess novel properties. The pharmacological advantages of a new combination of the benzodiazepine receptor agonist JM-1232(-) and propofol were investigated in mice. Male adult mice were administered JM-1232(-) or propofol or combinations of the two drugs intravenously. Loss of the righting reflex was evaluated as achieving hypnosis, and the time until recovery of the reflex was measured as hypnosis time. After determining the ED50, doses double and triple the ED50 of propofol were injected with JM-1232(-) to compare hypnosis time. The injections were repeated four times, and the hypnosis times were compared. Flumazenil was administered separately immediately after the last dose was injected. The ED50 values ([95% confidence interval]) for hypnosis were 3.76 [3.36-4.10] for JM-1232(-) and 9.88 [8.03-11.58] mg kg-1 for propofol. Co-administration of 0.5 and 1 mg kg-1 JM-1232(-) reduced the ED50 values of propofol to 1.76 [1.21-2.51] and 1.00 [0.46-1.86] mg kg-1, respectively. The drug combination for hypnosis produced a supra-additive interaction. Hypnosis time was significantly shorter in the groups given the mixtures compared to each hypnotic administered alone. After repeated injections, hypnosis time with the mixtures showed smaller prolongation than that with the hypnotic alone. Flumazenil completely restored the recovery time after anesthesia. The combination of JM-1232(-) and propofol showed a supra-additive interaction, and the reduced hypnotic dose contributed to a faster recovery even after multiple injections.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperazinas / Propofol / Isoindóis / Agonistas de Receptores de GABA-A / Hipnóticos e Sedativos Limite: Animals Idioma: En Revista: Exp Anim Assunto da revista: MEDICINA VETERINARIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Japão País de publicação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperazinas / Propofol / Isoindóis / Agonistas de Receptores de GABA-A / Hipnóticos e Sedativos Limite: Animals Idioma: En Revista: Exp Anim Assunto da revista: MEDICINA VETERINARIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Japão País de publicação: Japão