The antibacterial spectrum of cefroxadine was as wide as that of CEX, and its antibacterial effect was as strong as that of CEX or even 2-fold stronger against E.coli and Klebsiella.Cefroxadine was also proved to have stronger bactericidal or bacteriolytic effect than CEX and have better affinity with penicillin binding proteins.In clinical trials, an efficacy rate of82.7% was achived in a total of2,009cases of various infections analyzed.Cefroxadine displayed particularly good clinical and bacteriological effects for the infections of skin, soft tissues, respiratory tract and urinary tract.The rate of bacteria eradication in a total of1,410cases was 81.6%, showing good results against the bacteria such as S.aureus (83.9%, 167/199), E.coli (89.0%, 528/593), Klebsiella (78.0%, 78/100) and P.mirabilis (80.0%, 36/45).As for side effects, their incidence was a low of only2.3%, the main ones being eruption and gastrointestinal symptoms just as recognized in conventional cephalosporins, and none of them was serious.Abnormal laboratory test values were only increases in eosinophil, SGOT, S-GPT and Al-P values, and their incidence was low.
From these findings, we may say that the drug is an effective, safe, and useful antibiotic among all other orally administered cephalosporins.

抄録全体を表示

Fortimicin (KW4070) は広島市の土壌から分離された1) Micromonospora olivoasterosporaから得られた新しいAminoglycoside系抗生剤であり, グラム陽性菌および陰性菌に対して広範囲の抗菌スペクトラムを有しGentamicin (GM), Amikacin (AMK), Dibekacin (DKB) などと交叉耐性がなく第VIII脳神経に対する毒性が低いことが利点としてあげられる.
今回, 本剤について皮膚科学的に基礎的検討を行うとともに, 臨床評価も試みたのでその成績を報告する.

抄録全体を表示

Fortimicin (KW-1070), a new aminoglycoside antibiotic was administered to17patients suffering from surgical infections (peritonitis4cases, periproctal abscess5cases, subphrenic abscess3cases, suture abscess2cases, dead space infection2cases, perineal abscess1case). The results obtained are as follows.
1) Clinical effect of fortimicin was excellent in5, good in10and poor in2out of17cases.The effective rate was88.2% (15/17).
2) No significant side effect was observed.

抄録全体を表示

以前から, 外科領域における術後感染症の起炎菌としてグラム陰性桿菌の増加が注目されており, とくに消化管の術後における難治性感染症においては, その主体を占めていることが多い.
今回, Micromonospora olivoasterosporaにより産生される新しいアミノ配糖体系抗生剤Fortimicinの提供をうけた. 本剤はGentamicin (GM), Amikacin (AMK), Dibekacin (DKB) などと交叉耐性を示さないので, これら薬剤に耐性の諸菌にも抗菌性が期待されており, 従つて臨床効果も期待しうると考えられる. 本剤のもう1つの特長は, 聴器毒性がアミノ配糖体系抗生剤の中では最も弱く, また腎毒性も軽度なことである.
われわれが外科領域において屡々遭遇し, かつ術前の検査が不充分のまま手術に踏みきらざるを得ない消化管穿孔の緊急手術3症例に対して, 本剤単独で使用して, 若干の臨床成績を得たのでその結果について報告する.

抄録全体を表示

A dose of 200 mg or 300 mg of fortimicin was administered intramuscularly once a day for 4-6 days in 12 cases of otorhinolaryngological infections.
Clinical response obtained in these cases was excellent in 8 cases (66.7%), good in 3 cases (25.0%). The effective rate was 91.7%.
No side effect was observed in these 12 cases.

抄録全体を表示

Fortimicinは, 新しく開発されたアミノ配糖体系抗生物質で, Micromonospora olivoastmsporaにより産生され, その抗菌スペクトラムは広範囲であり, 特にSemtiamarcescens, BProteusinconstans等グラム陰性桿菌に対し強い抗菌力を示す.
今回我々は, Fortimicinの眼感染症に対する基礎的及び臨床的研究成績について報告する.

抄録全体を表示

A new aminoglycoside antibiotic, fortimicin, was administered intramuscularly at a dose of 200 mg, and the tissue distribution of the drug was investigated with time-course in the uterine fundus, uterine cervix, oviduct, endometrium and ovary.
Patients who required total hysterectomy or uterine appendices resection due to uterine myoma,etc. were studied.
The uterus levels of fortimicin were about 2 mcg/g at 2 hours after intramuscular administration in the uterine fundus and uterine cervix and reduced to trace after 8-9 hours.
The genital organs levels of fortimicin were ranged from 0.71 to 4.6 mcg/g at 1-3 hours after intramuscular administration and then reduced to the levels of 0.79 mcg/g in the oviduct, of 0.25 mcg/g in the endometrium and of 0.45mcg/g in the ovary after 5 hours.

抄録全体を表示

It is known that aminoglycoside antibiotics can produce theneuromuscular blockade which is mainly based on their antireleasing action of acetylcholine (Ach) at neuromuscular junctions1, 2). The neuromuscular blocking actions of kanamycin sulfate (KM) were firstly reported in vivo by TIMMERMAN et al.3) and its presynaptic blocking action was suggested by SINGHet al.4). Furthermore, pre-and post-junctional blocking actions of KM were clearly showed in vitro, and it was confirmed that KM can act preferentially at the presynaptic site and that the antireleasing action of KM can be completely antagonized by 3, 4-diaminopyridine in vitro2)3, 4-Diaminopyridine can reverse the neuromuscular depression by amikacin5), polymyxin B, lincomycin and clindamycin6) in vitro and 4-aminopyridine (4-AP) can reverselincomycin-pancuronium-induced neuromuscular blockade in man7). KM has not only the neuromuscular blocking action but also the cardiovascular depressive action8)as have the other aminoglycoside antibiotics9, 10, 11, 12, 13).
The aim of this study was to examine whether, as in vitro experiments of neuromuscular system, 4-AP could antagonize the neuromuscular and cardiovascular depressive actions of KM in anesthetized rats.

抄録全体を表示

B-Lactam系抗生物質とAminoglycoside系抗生物質との併用投与は臨床の場において広く行われており, CefotetanあるいはSisomicinについても併用投与が行われる可能性は充分あると考えられる. 今回, CefotetanおよびSisomicinを併用投与したときの両剤の生体内動態について検討するため, 両剤の混在下においてそれぞれの薬剤をBioassayにより分別定量する方法を検討した. その後, 両剤をラットに併用投与し, 両剤の血漿中および組織内濃度, ならびに尿中排泄について検討した.

抄録全体を表示

Cefotetan (YMO9330) およびSisomicinをラットに併用投与したときの両剤の生体内動態について前報1) で検討し, 両薬剤を併用投与しても各々の薬剤の動態は変化しないことを報告した. 今回, イヌに両剤を併用投与し, 両剤の血漿中濃度および尿中排泄を測定し, 併用投与したときの生体内動態を検討したので報告する.

抄録全体を表示

肺外科領域における抗生物質の使用は術後感染症に対する予防を主目的とする. このような目的において抗生物質の生体内移行, とりわけ病巣の存在する肺をはじめ胸腔内の種々の組織内濃度のパターンを知ることができれぽ術後感染対策として非常に有効と考えられる. もちろん予想される起炎菌の薬剤に対する感受性, 薬剤の排泄, 副作用などを考慮することはいうまでもない.
著者らは最近開発されたセフェム系抗生物質セフォチアム (略号: CTM, Pansporin®) の肺を主とする胸腔内組織濃度を知るため開胸肺手術症例について術中点滴静注し, 術中, 術後の血中濃度, 組織内濃度を測定したので若干の文献的考察を加えて報告する.

抄録全体を表示

感染症治療の際の抗生物質投与について, 3っの重要点の解答が要求される. 1) 薬剤は効果的であるか. 2) 安全であるか. 3) どのくらいの量を, どのように投与すべきか.
各種感染症の治療に際し, 副作用をみることなく, 有効体液, 組織濃度を一定時間保つ抗生物質の適量投与が不可欠となる. 不十分な投与量は無効であり, 過剰な投与は副作用をもたらす.
一般に抗生物質 (抗菌物質) の体液, 組織濃度が細菌の最小発育阻止濃度 (MIC) 以上になるよう投与される. 敗血症などの重症 (全身) 感染症には静菌的抗生物質よりも殺菌的抗生物質がより効果的とされている1). さらに, MICの5-10倍 (一般的に8倍) 以上の血中濃度を一定時間保つた場合, 一層治療的成功率が高いとされている2-6).
このような場合, いかに当該薬剤の原因菌に対するMICの8倍以上の血中濃度をうるよう抗生物質の投与量を決定するか臨床上重要な問題となる. 薬剤の抗菌力, 副作用, 毒性により, 投与量が左右される. いう迄もなく臨床分離細菌株の薬剤に対する感受性には非常に大きな差がある上に耐性菌株の存在が問題となる. 標準菌株あるいは一定場所の一定時期にえられた臨床分離株の薬剤に対する最小発育阻止濃度の画一的な感受性結果が特定の患者から分離された菌株に適応できないことも多い. しかし, 細菌学的検査の行われる前のBlind therapyにおいてはこのような成績が参考となる. 適切なる投与量を設定するためには当該原因菌に対する薬剤のMICと薬剤の薬動力学的特性を知る必要がある.
臨床検査室では日常のルーチン検査として, MIC測定をすることは非常に困難であるので, ルーチン検査のディスク感受性結果を上記目的に利用しえないかどうかの検討を本研究において行つた. ディスク感受性テストを注意深くコントロールした場合, その定量的評価から, MICの大体の値を推定でき7-10), 当該薬剤の生体内の薬動力学的知見から適否の決定, 投与量の設定が可能となる. こうして, Blind therapyからOptional therapyへと可及的速やかに移行しうる.
本論文においてはディスク感受性結果およびMIC値とその相関関係から, 投与量設定へのアプローチをセフォチアムを用いて提示した. 加えて各種セファロスポリン, ペニシリン, アミノグリコシド, テトラサイクリン, マクロライド, クロラムフェニコールなどへの各種臨床分離細菌感受性を比較してセフォチアム利用の臨床的意義を考察した.

抄録全体を表示

Midecamycin acetate is a diacetyl derivative of midecamycin1, 2), a macrolide antibiotic with a 16-membered ring, prepared by introducing acyl groups to 9 and 3position of its parent compound, as shown in Fig.1. 3) Its metabolic pathway and chemical structures of its metabolites have already been elucidated from a study on its metabolism4, 5)(Fig.1).
In the present study midecamycin acetate and its metabolites were evaluated bacteriologically both in vitro and in vivo with following results.

抄録全体を表示

9, 3-Diacetylmidecamycin (MOM) は, 明治製菓株式会社により開発されたMacrolide系薬剤であり, Midecamycin (MDM) の誘導体である. Macrolide系薬剤の適応症は腸球菌以外のGram陽性球菌感染症であるが肺炎球菌や溶連菌に対する第1次選択剤は, β-Lactam剤であると思われ, 本系の薬剤はむしろ第2次選択剤である. 本系薬剤が第1次選択剤として考えられる小児科領域の感染症では, マイコプラズマ肺炎, 百日咳およびβ-Lactam剤耐性のブドウ球菌感染症が主なものである.
MOMはStaphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Bordetella pertussisに対してはMDM, Josamycin (JM) とほぼ同様の抗菌力を示すが, 嫌気性菌およびMycoplasma pneumoniaeに対しては優れた抗菌力を示すといわれ, 血中濃度推移についてもMDMよりも高濃度を維持するといわれている.
今回, 我々はMOMについて, その抗菌力, 体内動態および臨床効果ならびに副作用の検討を行つたので報告する.

抄録全体を表示

Cefmetazole (CMZ) は三共により開発されたβ-ラクタマーゼに強い抵抗性を示すセファマイシン系抗生物質1, 2) で, 第2世代のセファロスポリン系 (CEPs) 抗生物質とも呼ばれている. 本剤は幅広い抗菌スペクトルを有し, 細胞壁合成阻害作用により, 増殖期の菌に対し殺菌的に作用する. すでに, 内科, 外科, その他の領域においてCMZは優れた臨床効果を示すことが報告3) されている.
今回, 昭和56年2月から昭和56年9月まで各機関において, 本剤をStaphylococcus, streptococcusなどの化膿球菌性皮膚感染症に対して試用し, 本剤の有効性ならびに安全性を検討する機会を得たので報告する.

抄録全体を表示

We had reported the fundamental study on the utility of a new cephem antibiotic, cefmetazole (CMZ).On the basis of the results we administered CMZ to patients to investigate its clinical utility in this study.
1.CMZ was administered to 53patients including 4 infants.They consisted of 30cases of acute tonsillitis, 10 of peritonsillar abscess, 10 of laryngitis or pharyngitis, and 3 of sinusitis.
2. One or 2 g CMZ was administered to an adult patient except for 1 case and0.5g to an infant patient once or twice daily for at least 3days. The method of administration was one shot intravenous injection, intravenous drip infusion or intramuscular injection.
3.The strict criteria for evaluating the efficacy of a drug were made and used for judging the efficacy of CMZ.
4.CMZ was clinically effective in 100% of patients with acute tonsillitis, 100% of those with peritonsillar abscess, 90% of those with laryngitis or pharyngitis, and 67% of those with sinusitis.
5.Bacteriologically, a single sort of bacerium was isolated in most cases of acute tonsillitis, laryngitis and pharyngitis and in the half of cases of peritonsillar abscess. Two and more sorts of bacteria were isolated in the other cases. The main bacteria isolated were β-Streptococcus, S. pneumoniae and H. influenzae. Anaerobic bacteria, mostly Peptococcus spp. and Peptostreptococcus spp., were detected in peritonsillar abscess.
6.The clinical results agreed with the clinicobacteriological results. All the bacteria detected before treatment of CMZ disappeared. CMZ also acted effectively in cases in which H.influenzae was suspected to be a causative organism.
7.The present results of CMZ treatment were similar to those of cefazolin (CEZ) treatment published so far.
8. Thus, CMZ was confirmed fundamentally and clinically to be a very useful drug for infection of the upper respiratory tract.

抄録全体を表示

セブメタゾール (CS-1170, 以下CMZ) は, 1976年三共株式会社において開発されたCephamycin系抗生物質1) で, 構造式はFig.1のとおりである.

抄録全体を表示

The ototoxicity of netilmicin (NTL) in pregnant guinea pigs (Hartley strain) and the newborn was examined and compared to that of gentamicin (GM).
NTL was administered intramuscularly at dose of90mg/kg to pregnant guinea pigs from day0today35of pregnancy (the early period of pregnancy) or from day42of pregnancy to1day prior to delively (the late period of pregnancy). GM at dose of45mg/kg or physiological saline were administered intramuscularly to pregnant guinea pigs during the late period of pregnancy. Four of5dams given NTL during the early period of pregnancy, 4of7dams given NTL during the late period of pregnancy, and2of4dams given GM during the late period of pregnancy died.
No pinna reflex loss in frequency range from2to20KHz were detected in mother guinea pigs treated with NTL either during the early period of pregnancy or during the late period of pregnancy.
GM caused a loss of pinna reflex at20KHz in mother guinea pigs treated during the late period of pregnancy. Histopathologically, no damages were detected in the cochlea of mother guinea pigs treated with NTL during the early or late period of pregnancy, whereas slight scattered loss of hair cells was seen in the vestibulum.However, GM at dose of45mg/kg, caused an incomplete scattered loss of outer hair cells in the spiral organ, moderate atrophy of the spiral ganglion cells and a partial loss of hair cells in the vestibular organs in mother guinea pigs treated during the late period of pregnancy. In newborn guinea pig from the pregnant one treated with NTL during the early period of pregnancy, there was no loss of pinna reflex. The same results were obtained in newborn guinea pigs from the pregnant ones treated with either NTL or GM during the late period of pregnancy.No histopathological damages were detected.
The present study suggests that NTL has a minimal effect on the auditory and vestibular organs in pregnant guinea pigs and the newborn and is considered to be1of the aminoglycosides with low ototoxic potential.

抄録全体を表示

近年, 急性淋疾は, 国際交流の高まり, 不純性交遊技, ペニシリン, テトラサイクリンなどの耐性菌の出現1) などの要因から, 増加傾向が指摘されている2).女子における淋疾の淋菌性頸管炎においては, 定型的な症状をともなわないこともあり, 慢性化すると, その頸管帯下は, 淋菌性以外の原因による帯下との区別がつけ難いなどから, 感染源を温存する場合もある2).
淋疾に対する治療薬としては, ペニシリン系抗生物質が今日においても基本とされているが3), ペニシリン, テトラサイクリンなどの耐性菌の出現1), ペニシリン療法の有効性の低下4), さらには, ペニシリンによるアナフィラキシー・ショックのために, 第一線の診療施設では, 選択剤に苦慮することも多い.
そこで, 私たちは, 1回量として比較的大量に筋注が可能であることから, 長時間の血中濃度および体内で有効活性濃度を持続させることができるSpectinomycin (Trobicin®, 日本アップジョン, 以下SPTMと略) および経口投与が可能なAmpicillin (Viccillin, 以下ABPCと略) の併用療法について一定の検討を行つたので, 報告する.
尚, 本検討については, 子宮頸管分泌物中の淋菌の検索の他に, 好気性菌, 嫌気性菌の検索, 検出菌のSPTM, ABPCのMICおよびSPTM+ABPCの試験管内抗菌協力作用等の細菌学的検討を合わせて行つたが, 本稿では, 淋菌に関する細菌学的検討成績だけを報告し, 他の成績は, 別稿7) として扱つたことを付記しておきたい.

抄録全体を表示

Aminoglycoside系 (AGs) 抗生物質の投与経路は, 従来から菌血症や筋注投与不能例を除けば, 筋注投与だけに限定されてきた. しかし最近では, 本剤の体液内濃度測定法や薬動力学的研究等の基礎的分野での研究が飛躍的に進み, 安全性の確認がより的確にかつ迅速に行えるようになつてきた。こうしたことを背景に, 多方面にわたる感染症の治療分野で, AGsの点滴静注投与 (Dripinfusion, 以下d.i.) が試みられている.
筆者はこうした多くの報告を参考として, AGsのうちGentamicin (GM) を用い, 一部の症例で血中濃度を測定した上で, 慢性複雑性尿路感染症を対象に, d. i. による治療を行い, 臨床成績と安全性について検討を行つたので報告する.

抄録全体を表示

白血病自体による宿主免疫能の低下に加えて, 最近の抗白血病剤による多剤併用寛解導入療法によつてもたらされる造血能の低下, とりわけ好中球の減少は, 感染必発の条件であり, このような特殊条件下で発生する急性白血病治療中の随伴感染症に対しては, 一般の感染症とは異なる治療法が要求される.
既に諸家が指摘するように1-3), 本感染症はグラム陰性菌, 真菌などいわゆるOPPortunistic infectionが主体であり, しかも急性白血病の死因の70%以上が感染症といわれ, Bioclean roomの設置など, その対策が切望されている. 当大学においても2年前から無菌室が設置され呼吸器感染の減少などその有効性について報告してきた3, 4).
今回, 私共は, 従来のAminoglycosideと比較し, 耳および腎の毒性が低いといわれる5) Amikacin (AMK) の大量 (600-1,200mg今日) 点滴静注投与を中心とした多剤併用療法を, 急性白血病治療中に合併した感染症, 特に敗血症など重症感染症の治療に使用し, 評価し得る成績を得たので報告する.

抄録全体を表示

The study group was organized to evaluate the usefulness of cefmenoxime (CMX) injection, anew synthetic cephalosporin, for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made by the society and the following results were obtained.
1. The peak distribution of CMX's MIC for E. coli, Klebsiella sp., Enterobacter sp., Bacteroides sp. and Peptococcus sp.isolated from obstetrical and gynecological infections with relatively high frequencies are 0.1, ≤0.05, 0.2, 3.13, 1.56μg/ml, respectively, with an inoculation of10⁸cells/ml.
2.When1g of CMX is administered by intravenous drip infusion for1hour, the maximum concentrations in various tissues of female genital organs were as follows: 14.2 and 13.2μg/g in ovary and oviduct, respectively, at1.20 hours after the start of administration, and 16.9 and 26.3μg/g in corpus uteri and cervix uteri, respectively, after 1 hour. As for the transfer to the exudate in the pelvic dead cavity, the peak concentration was 15.6μg/ml after 2.13 hours.
3.In the clinical studies, CMX was given to 258 cases with female genital organ infections and others. As for the clinical effects, with exclusion of 3 cases in which other antibiotics are concomitantly used, responses were excellent in 76 cases, good in 162 cases and poor in 17 cases, among 255 cases in total.The efficacy rate was93.3%.
The efficacy rates by diseases were 97.1% (68/70) for intrauterine infections, 88.8% (79/89) for intrapelvic infections, 98.4% (62/63) for adnexitis, and 100% (23/23) for infections of external genital organs.As for the clinical effects on causative bacteria, the efficacy rates were 100% (19/19) for single infections due to Gram-positive bacteria, 94.8% (55/58) for single infections due to Gram-negative bacteria, and 88.2% (15/17) for single infections due to anaerobic bacteria.And its efficacy rates were 89.6% (69/77) for mixe infection cases.
Side effects were observed in2cases (0.8%);1case with eruption, and 1 case with diarrhea and and vomiting. As for abnormal laboratory findings, lower white blood cell count was observed in2 cases and elevation of the values regarding hepatic functions in9cases. All cases were returned to the normal after the completion of the administration.
Cefmenoxime showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infections in the field of obstetrics and gynecology, and it has been concluded that cefmenoxime will be a useful addition to the antibiotics for the therapy of these infections.

抄録全体を表示

Cefoxitin (CFX) was administered to 12 patients for evaluation of clinical effects of CFX against secondary infections complicated with hematopoietic malignancies, and the following results were obtained.
1. The clinical effects were excellent in 1 and good in 8 out of 11 cases with efficacy rate of 81.8%. Out of 12 cases treated with CFX, 1 case was excluded from clinical evaluation because of prophylactic use.It is noted that all cases with pyelitis showed good response to CFX.
2. The serum levels of CFX were determined in 1 patient with renal failure. After intravenous drip infusion of 2 g in 200 ml of glucose solution, the serum concentrations were 67.2μg/ml and 7.53μg/ml at 14 hours and 24 hours (after hemodialysis), respectively.
3. No side effects attributed to CFX were observed.
These results indicate that CFX is an effective and safe antibiotic for the treatment of severe infections accompanying hematopoietic malignancies.

抄録全体を表示

近年, 各種疾患に対する外科の進歩には著しいものがあり, これには種々の検査法の進歩, 手術手技の向上, 抗生剤の進歩, 高カロリー輸液等による術前, 術後の管理面での進歩に負うところが大きい. このためRiskの高い患者, 高齢者等に対して積極的に手術が施行され, 手術成績も向上して来ているが, 術前, 術後の感染症は, その手術成績に影響を及ぼすだけではなく時には患者を重篤な状態に至らしめる. 他方抗生剤の進歩は耐性菌の出現をもたらし, そのためより的確な抗生剤の使用が要求される.
今回, われわれは, 嫌気性菌を含むGram陽性菌および陰性菌に強い抗菌力を持っCephamycin系抗生物質Cefoxitin (CFX) を主として消化器外科領域の術後感染症および感染予防に使用し, その臨床的効果, 細菌学的効果および副作用について検討を行つたので報告する.

抄録全体を表示

近年, 抗生剤の開発にはめざましいものがある. 一方, 産婦人科領域における感染症も耐性菌の増加や菌交代現象, 常在菌による混合感染などが問題となつてきた. とくに, グラム陰性桿菌や嫌気性菌による感染症の増加が注目されている.
Cefoxitin (商品名: マーキシン注射用, 以下CFX) は, 1972年米国Merck Sharp & Dohme Research Laboratoriesにより開発された最初のCephamycin系抗生物質である. グラム陰性菌からグラム陽性菌にわたる広い抗菌スペクトラムを有しており, とくに産婦人科感染症と関連深いEscherichia coliなどのグラム陰性桿菌, および偏性嫌気性菌 (Bactmides fragilis) に対して強い抗菌活性を示すのが特徴とされる. 今回, 術後感染予防ならびに主として骨盤内感染に対するCFXの臨床効果を検討したので報告する.

抄録全体を表示

General pharmacological effects of KW-1414, a new orally-active antifungal agent, were studied, and the following results were obtained.
1. KW-1414400mg/kg, p.o.caused significant depression on spontaneous activity, prolongation of pentobarbital sodium induced hypnosis, hypothermia and augmentation of reserpine-induced hypothermia in mice.In addition, KW-1414400mg/kg, p.o.showed slight muscle relaxant and anticonvulsive activities in mice.Ptosis and slight passivity were also observed at this dose.But KW-1414100mg/kg, p.o.caused only augmentation of reserpine-induced hypothermia, and any of the above effect was not found at the dose of25mg/kg, p.o.KW-141410mg/kg, i.v.had no effect on body temperature in rats and mice, on spontaneous EEG in rabbits and on spinal reflex in cats.
2. KW-14143mg/kg, i.v.lowered femoral blood pressure, increased femoral blood flow transiently and decreased heart rate in dogs.In isolated atria of guinea pigs, KW-1414 10^-4M decreased atrial rate and atrial contractile force significantly.But KW-1414had no effect on respiratory rate, ECG and blood pressure reflex induced by bilateral carotid artery occulusion and asphyxia in dogs at the dose of10mg/kg, i.v.KW-1414100mg/kg, p.o.also had no effect on heart rate in conscious rabbits. And KW-1414 10^-4m did not influenced hemolysis and hemopexis in rabbit blood.
3. KW-1414caused dose-dependently contraction of nictitating membrane induced by adrenaline hydrochloride injection, but had no effect on that induced by electric stimulation in cats.And KW-1414 10mg/kg, i.v.had no effect on pressure-response induced by noradrenaline or acetylcholine chloride injection.
4. KW-1414at high doses had non-specific depression on contraction of isolated smoo th muscles induced by various agonists and on spontaneous movement of isolated smooth muscles. And KW-1414 10^-4m caused relaxation of isolated tracheal smooth muscle of guinea pigs.But KW-1414had no effect on intestinal propulsion in mice.
5. KW-1414 10^-4M augmented the contraction of isolated phrenic nerve-diaphragm preparation induced by electric stimulation in rats.But KW-141410mg/kg, i.v.scarcely influenced the contraction of tibialis anterior muscle-sciatic nerve preparation induced by electric stimulation in rabbits.
6. KW-1414decreased urinary volume and electrolyte excretion in rats dose-dependently, while it had no local anesthetic activity in guinea pigs.And KW-1414had no effect on gastric secretion, on spontaneous bile excretion in rats and on dermal tissue permeability in rabbits.

抄録全体を表示