VOL.32 S-3 CHEMOTHERAPY
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1 CHEMOTHERAPY APR. 1984
2 VOL.32 S-3 CHEMOTHERAPY
3 CHEMOTHERAPY APP Fig. 1 Characteristic of blood pressure response H: Peak pressor response (mmhg) of pressor response above 50% level (see)
4 VOL.32 S-3 CHEMOTHERAPY Table 1 Effect of AT on general behavior in mice Each value represents score of positive/ tested; 1= 0/ 5, 3= 1/ 5, 5= 2/ 5, 7= 3/ 5, 8= 4/ 5 and 9= 5/ 5
5 CHEMOTHERAPY APR Fig. 2 Effect of AT on spontaneous locomotor activity in mice (by Animex) Time after administration (min) Table 2 Effect of AT on rotarod performance in mice Each value represents positive/ tested.
6 VOL.32 S-3 CHEMOTHERAPY Table 3 Effect of AT on hexobarbital narcosis in mice Significant difference from control (vehicle): * p<0.05,**p<0.01 Fig. 3 Effect of AT on pentetrazol- and strychinine- induced seizure in mice
7 CHEMOTHERAPY APR Table 4 Effect of AT on acetic acid- induced writhing syndrome in mice Table 5 Effect of AT on body temperature in rats Significant difference from control:* p<0.05,** p<0.01 Fig. 4 Effect of AT on reserpine- induced hypothermia in mice C: Control, 1:125mg/ kg po, 2: 250mg/ kg, 3: 500mg/ kg, 4: 1,000mg/ kg, I: Imipramine, a): Before, b): After 4 hr, significant difference from control:
8 CHEMOTHERAPY Fig. 5 Effect of AT on one- way active avoidance in mice Fig, 7 Effect of AT on spontaneous EEG activity in cat Before 10 min after AT mg/kg i.v. (cumulative) Time after administration (hr) 15 min after AT mg/kg i.v. (cumulative) Fig. 6 Effect of AT on spontaneous EEG activity in cats L-ASS: Left anterior suprasylvian gyrus L-PSS: Left posterior suprasylvian gyrus R-HIP: Right dosal hippocampus ECG: Electrocardiogram (Lead II) Fig. 8 Effect of AT on evoked EMG in rats Time after administration (min) Time after administration (min)
9 CHEMOTHERAPY Table 6 Effect of AT on blood pressure and heart rate in normotensive rats Each value represents mean } S. E. Significant difference from control (Before value): * p< 0.05, ** p< 0.01
10 CHEMOTHERAPY Fig. 9 Effect of AT (10 mg/ kg, i.v.) on respiration, heart rate, nictitating membrane and blood pressure in anesthetized cats Time after administration (min) Fig. 10 Effect of AT (30 mg/ kg, i.v.) on respiration, heart rate, nictitating membrane and blood pressure in anesthetized cats Time after administration(min) Fig. 11 Effect of AT on respiration (Resp), heart rate (HR), blood pressure (BP) and carotid blood flow (CBF) in anesthetized dog Dog 9kg male
11 CHEMOTHERAPY Fig. 12 Effect of AT on ECG (lead II) in anesthetized dog AT mg/ kg iv AT mg/ kg iv
12 CHEMOTHERAPY Fig. 13 Effect of AT on spontaneous movement of isolated guinea- pig atrium Fig. 14 Effect of AT on perfusion of isolated rabbit ear vessel
13 CHEMOTHERAPY Fig. 15 Effect of AT on response of nictitating membrane (NM) induced by electrical stimulation (ES) of superior cervical nerve in anesthetized cat Fig. 16 Effect of AT on response of blood pressure (BP) and nictitating membrane induced by adrenaline (Ad) in anesthetized cat Fig. 17 Effect of AT on response of blodd pressure (BP) and heart rate (HR) induced by electrical stimulation (ES) of cervical vagus nerve and histamine (Hist) in anesthetized cat
14 CHEMOTHERAPY Table 7 Effect of AT on response of blood pressure induced by noradrenaline, tyramine, carotid occlusion and acetylcholine in anesthetized cats Each value represents mean }S. E. Significant difference from control value:* p< 0.05 H: Peak pressor response (mmhg) D: Duration of pressor response above 50% level (sec)
15 CHEMOTHERAPY Table 8 Effect of AT on contraction of isolated guinea- pig ileum induced by acetylcholine histamine (Hist), bradykinin, serotonin and BaCl2 (ACh), Each value represents mean }S. E. Conc.: Concentration, -: Potentiation, (P): Phasic effect Table 9 Effect of AT on responses to adrenaline in isolated guinea- pig was deferens and trachea Each value represents mean } S. E. Conc.: Concentration,-: Potentiation
16 CHEMOTHERAPY Fig. 18 Effect of AT on response to noradrenaline (NA) in isolated guinea- pig atrium AT g/ ml Fig. 19 Effect of AT on response to acetylcholine (ACh) in isolated guinea- pig atrium AT g/ml
17 CHEMOTHERAPY Fig. 20 Effect of AT on contraction of isolated rabbit aorta induced by noradrenaline Table 10 Effect of AT on passage of charcoal meal in small intestine of mice Significant difference from control:**p< 0.01 Concentration of npradrenaline (M) Fig. 21 Effect of AT on spontaneous motility of isolated rabbit ileum Fig. 23 Effect of AT on spontaneous motility of isolated gestational rat uterus Fig. 22 Effect of AT on spontaneous motility of isolated non-gestational rat uterus
18 VOL.32 S-3 とん ど影 響 を 及ぼ さな か った が,1,000mg/kg投 か った(Fig.24) 2)局 181 CHEMOTHERAPY AT-2266は, g/mlの 与 では, 6時 間 尿 に お い て,尿 最 の 軽 度 な 減 少,尿 中 へのNa+排 所麻 酔作用 お よび局 所 刺 激 作 用 生 理 食 塩 液 溶 液 の0.2 泄 最 の 軽 度 な減 少お よびNa+/K+値 の 低 下(p<0205で ml点 眼 で,ウ サ ギ眼 粘 膜 に お け る角 膜 反 射 の 抑制 を指 有 意)を 示 した しか し,そ の後 にお いて 回 復 し,24時 間 標 とす る局所(表 面)麻 酔作 用 な らび に 眼 粘 膜 に対 す る 尿 で は いず れ もほ とん ど影 響 が 認め られ な か った(Fig. 刺激作 用を示 さな か った 25) 3)ラ ッ トの尿 量お よび尿 中電 解 質 排 泄 に 及 ぼす 影 轡 AT-2266は,10お よび100mg/kg経 の尿量 お よび尿 中 へ の電 解 質(Na+お 口投 与 で ラ ッ ト よびK+)排 泄 にほ 4)麻 酔 ラ ッ トの 胆 汁 分泌 に及 ぼ す 影 響 AT-2266は,10,30お よび100mg/kg皮 麻 酔 ラ ッ トの 胆 汁 分 泌量 にほ とん ど影 御 を 及ぼ さな か っ Fig. 24 Effect of AT-2266 on neuromuscular junction (sciatic nervegastrocnemius muscle) in anesthetized rat Fig. 25 下 投 与 で, Effect of AT-2266 on urine volume and electrolytes (Na+ and K+) excretion in saline-loaded rats C:Control(vehicle),1;AT mg/kgpo, 2:AT/ mg/kgpo,3:AT-22661,000mg/kgpo, Significantdifferencefromcontroll*p<0.05.
19 CHEMOTHERAPY Table 11 Effect of AT on bile secretion in anesthetized rats Each value represents mean }S. E. Fig. 26 Effect of AT on gastric juice secretion and acid output in pylorus ligated rats (5 hr ligation) C : Control (vehicle), 1: AT mg/ kg po, 2: AT mg/ kg po, 3: AT ,000 mg/ kg po. Significant difference from control : * p< 0.05,** p< 0.01.
20 CHEMOTHERAPY 1) KOGA, H.; A. I TOM, S MURAYAMA, S. SUZUE& T. IRIKURA: Structure-activity relationships of antibacterial 6. 7-and 7, 8- disubstituted 1- alkyl- 1, 4- dihydro- 4- oxoquinoline-3-carboxylic acid. J. Med. Chem. 23: 1358 ` ) IRWIN, S.: Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and phisiologic state of the mouse. Psycopharmacologia (Berl) 13, , ) DANHAM, N.W& T.S. MIYA: A note on a simple apparatus for detecting neurological deficiti rats
21 CHEMOTHERAPY and mice. J. Am. Pharm. Assoc, Sci. Ed. 46: 208 ` 209, ) SNIDER, R.S& W.T. NIEMER : A stereotaxic atlas of the cat brain. University of Chicago Press, Chicago, ) ITO, T& M. SHIMIZU : Effects of chlorpromazine, imipramine and baclofen on the spinal polysynaptic reflex in acute, chronic and 6- hyroxydopaminetreated spinal rats. Japan J. Pharmacol. 32: 1125 ` 1133, ) MATSUO, S& N. TODA: The influence of desmetylimipramine on the chronotropic response to endo. genous and exogenous noradrenaline in the isolated atria. Brit. J. Pharm Chemoth. 32: 473 `482, 1968 GENERAL PHARMACOLOGICAL PROPERTIES OF AT YUKIO MATSUNO, NAOKO TAIRA and TOSHIAKI KADOKAWA Research and Development Division, Dainippon Pharmaceutical Co., Ltd. Pharmacological properties of AT- 2266, a new antibacterial agent, were investigated with the following results. (1) By oral administration, AT-2266 did not show significant pharmacological effects except for a few experi. mental items such as potentiation in hexobarbital narcosis in mice and a slight decrease in acid output in rats. (2) By intravenous administration, AT caused hypotension, decrease in heart rate and inhibition in respiration in anesthetized cats. In addition, minor changes were observed in ECG pattern and carotid blood flow in anesthetized dogs. (3) EEG pattern, responses of blood pressure and heart rate induced by autonomic substances in cats were slightly affected by intravenous administration of AT Moreover minor changes were observed in respiration, ECG pattern, tone of nictitating membrane. But no appreciable effects was observed in contraction on skeletal muscle. (4) In the experiments with isolated organs, AT did not show appreciable effects except for a slight changes in rabbit ileum, rabbit ear vessel, guinea-pig atrium and rat uterus. From these results, it could be considered that pharmacological properties of AT-2266 closely resembles those of piromidic acid (PA) and pipemidic acid(ppa).
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