non-dihydropyridine誘導体である新規カルシウム拮抗薬Ro40-5967の血管拡張作用をラット腸間膜動脈灌流標本を用いて検討した.Ro40-5967 10-6Mとニフェジピン10-7MはKCl(20,40,60μmol)による一過性の血管収縮を同程度抑制した,Ro40-5967(10-6M)はノルエピネフリン(200,300,400ng)投与および経壁電気刺激(4,8,10Hz)による一過性の血管収縮反応を有意に抑制した.これに対しニフェジピン10-7Mでは有意な抑制作用は認められなかった.ノルエピネフリン(200,300,400ng)および経壁電気刺激(4,8,10Hz)による血管収縮反応はエンドセリン-1 10-10Mによって著明に増強された.この増強反応に対してRo40-5967 10-6Mはこれを完全に抑制した.これに対しニフェジピン10-7Mは抑制作用を示さなかった.Ro40-5967はラット腸間膜動脈灌流標本において同程度のKCl収縮抑制を示す濃度を用いた場合,ニフェジピンと比べてノルエピネフリン投与,経壁電気刺激およびそれらのエンドセリン-1による収縮増強反応に対し強い抑制作用を示した.

10.1254/fpj.105.171

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Citations (2)

DRUG-INDUCED INHIBITION OF GUINEA PIG PLATELET AGGREGATION UNRELATED TO THEIR β-ADRENOLYTIC ACTIONS

The Japanese Journal of Pharmacology (1983)

Mieko IWAMURA Tsutomu Ishimori Masao MAKING Kikuo Yasuda Akihiro Izumi

Inhibitory actions on adenosine diphosphate (ADP)-induced platelet aggregation of atenolol, dl- and d-D-32, IPS-339, pindolol and propranolol were investigated in guinea pigs for the purpose of obtaining a clue about a possible mechanism for the disaggregatory phenomenon of β-adrenoceptor blocking agents. The effects of verapamil and procaine on guinea pig platelet aggregation were also examined. All of these agents including verapamil and procaine showed a dose-dependent inhibitory effect on platelet aggregation, and their relative potencies determined on the basis of the molar concentrations producing a 50% inhibition of ADP-induced aggregation were in descending order: IPS-339>propranolol>verapamil>dl-D-32⩷d-D-32> pindolol > procaine>atenolol. This order of relative potencies of the inhibitory actions of these test compounds on platelet aggregation was well correlated to those of local anaesthetic action in guinea pigs (r=0.932, P<0.01) and lipophilicity (r=-0.899, P<0.01), while it did not agree with the orders of potency of β-adrenoceptor blocking action, intrinsic sympathomimetic action and vasodilator action. From these results, it may be reasonable to propose that inhibitory actions of β-adrenoceptor blocking agents and local anaesthetics on platelet aggregation are caused through the same mechanism or through a very similar one.

Pindolol

Atenolol

Practolol

Mechanism of Action

10.1016/s0021-5198(19)52559-8

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Citations (1)

INHIBITION OF EXCITATION-CONTRACTION COUPLING IN THE VENTRICULAR MYOCARDIUM OF THE DOG BY SKF 24260

Clinical and Experimental Pharmacology and Physiology (1976)

Norio Taira Norio Himori Yutaka Imai

1. The effects of SKF 24260 on the coronary vasculature and on the electrical and mechanical activities of the ventricular myocardium were studied by the use of papillary muscle preparations of the dog. The preparation was cross-circulated from a donor dog through the anterior septal artery, and driven at a rate of 120 beats/min. Drugs were injected into the anterior septal artery. 2. SKF 24260, in doses of 0-01-100 mug, caused a dose-dependent increase in the rate of blood flow through the anterior septal artery; the mean dose producing a 100% increase in blood flow rate was about 0-7 mug. 3. SKF 24260 in doses of 0-01-0-03 mug produced a slight increase in developed tension of papillary muscles. With 0-1-0-3 mug of SKF 24260 the increase was preceded by a transient decrease, and with doses larger than 1 mug the drug caused a dose-dependent decrease. The mean dose producing a 50% decrease in developed tension was about 2-8 mug. 4. SKF 24260 failed to affect the amplitude and shape of bipolar electrograms even in doses of 39-100 mug which completely abolished the developed tension. 5. The decrease in the developed tension caused by SKF 24260 was overcome by exogenous calcium; the increase in the developed tension in response to exogenous calcium was antagonized by SKF 24260. 6. These results indicate that the dilator action of SKF 24260 on the coronary vasculature is more prominent than the negative inotropic action on the ventricular myocardium, and suggest that the negative inotropic action is probably due to antagonism of the role of calcium in excitation-contraction coupling.

Papillary muscle

Dilator

10.1111/j.1440-1681.1976.tb00638.x

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Citations (14)

Dextrorphan attenuates the behavioral consequences of ischemia and the biochemical consequences of anoxia: possible role of N-methyl-d-aspartate receptor antagonism and ATP replenishing action in its cerebroprotecting profile

Psychopharmacology (1993)

Norio Himori Yushiro Tanaka Mitsue Kurasawa Kenichi Mishima Nobuhide Akaike

Dizocilpine

10.1007/bf02245517

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Citations (6)

Negative and positive effects of intracerebroventricular scopolamine on memory in mice undergoing passive avoidance and escape tests

Brain Research Bulletin (1994)

Masaharu Nakajima Akio Inui Masaki Miura Yoshiaki Hirosue Minoru Okita

Scopolamine

Locomotor activity

Avoidance response

Water maze

10.1016/0361-9230(94)90032-9

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Citations (7)

MAO Inhibitors, Clorgyline and Lazabemide, Prevent Hydroxyl Radical Generation Caused by Brain Ischemia/Reperf usion in Mice

Pharmacology (1995)

Tatsuya Suzuki Nobuhide Akaike Kenichi Ueno Yushiro Tanaka Norio Himori

The effects of clorgyline, the MAO-A inhibitor, and lazabemide, the MAO-B inhibitor, on the levels of the hydroxyl radicals appearing in the cerebral ventricles of mice during brain ischemia/reperfusion were examined by using a salicylate trapping method. The amount of hydroxyl radicals formed peaked at 20 min after reperfusion (approximately 150% vs. basal level). The dopamine level markedly increased shortly after the initiation of an ischemic insult and thereafter waned. By contrast, the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) level decreased during a 40-min period of ischemia, gradually returning to the preischemic basal level upon reperfusion. The ischemia reperfusion-induced hydroxyl radical generation was attenuated by 3 mg/kg of clorgyline and lazabemide. Furthermore, mice pretreated with these MAO inhibitors showed decreased DOPAC levels in comparison with those of their respective vehicle-treated control groups; recovery of the reduced DOPAC level was also delayed. In conclusion, it is likely that both type A and type B MAOs participate in the generation of hydroxyl radicals during brain ischemia/reperfusion. This finding suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury.

Clorgyline

Hydroxyl radical

10.1159/000139304

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Citations (36)