Electroencephalographic and cardiovascular effects of milnaciplan hydrochloride (TN-912), a novel antidepressant.
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- KAWASAKI Hiromu
- Department of Pharmacology, Miyazaki Medical College
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- YAMAMOTO Ryuichi
- Department of Pharmacology, Miyazaki Medical College
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- URABE Masanobu
- Department of Pharmacology, Miyazaki Medical College
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- NUKI Chikako
- Department of Pharmacology, Miyazaki Medical College
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- TASAKI Hirotoshi
- Department of Pharmacology, Miyazaki Medical College
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- TAKASAKI Koichiro
- Department of Pharmacology, Miyazaki Medical College
Bibliographic Information
- Other Title
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- 新規抗うつ薬Milnacipran hydrochloride(TN‐912)の脳波および循環器に対する作用
- シンキ コウ ウツヤク Milnacipran hydrochloride T
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Abstract
The electroencephalographic (EEG) and cardiovascular effects of milnaciplan hydrochloride (TN-912) were compared with those of imipramine (IMP) and maprotiline (MPT) in rats, guinea pigs and dogs. In conscious rats with chronic electrode implants, TN-912 (10 ?? 100 mg/kg, p.o.) had little effect on either the EEG activity or the EEG arousal response to auditory stimulation (2000 Hz). Both IMP (10 ?? 100 mg/kg, p.o.) and MPT (10 ?? 100 mg/kg, p.o.) tended to increase the drowsy EEG pattern period in the cortical and hippocampal EEG and inhibited the EEG arousal response to auditory stimulation. In conscious rats with a chronic arterial catheter, TN-912 (100 mg/kg, p.o.) slightly elevated the mean blood pressure (MBP) and decreased the heart rate (HR), while both IMP (10 ?? 100 mg/kg, p.o.) and MPT (10 ?? 100 mg/kg, p.o.) dose-dependently increased MBP and HR. In anesthetized dogs, i.v. injection of TN-912 (1 ?? 10 mg/kg), IMP (0.3 ?? 10 mg/kg) and MPT (1 ?? 10 mg/kg) produced a dosedependent fall in MBP. IMP and MPT but not TN-912 dose-dependently increased HR. TN-912 did not show typical effects on femoral blood flow. TN-912 (30 mg/kg) had little effect on lead II electrocardiogram (ECG), while IMP and MPT markedly increased height of the T-wave on ECG. In the in vitro study with the isolated guinea pig atrium, TN-912 caused a slight positive inotropic and negative chronotropic effect, while both IMP and MPT showed marked negative inotropic and chronotropic actions. These results suggest that TN-912 has less EEG effect and cardiac toxicity, indicating that TN-912 may be safe in clinical use.
Journal
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- Folia Pharmacologica Japonica
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Folia Pharmacologica Japonica 98 (5), 345-355, 1991
The Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390001204271442688
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- NII Article ID
- 130000758808
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- NII Book ID
- AN00198335
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- ISSN
- 13478397
- 00155691
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- NDL BIB ID
- 3750369
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- PubMed
- 1813366
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed