[Pharmacology of the brain].
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Biomedical subjects
Publications and source records attributed to Y Hagihara.
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In media containing collagen as the nitrogen source, the pathogenic yeast Candida albicans secreted a collagenolytic enzyme. Purification of the enzyme from a culture filtrate was achieved by DEAE-Sephacel chromatography at pH 6.7. The molecular weight was found to be 46,000 by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the isoelectric point was at pH 4.2. The pH optimum lay between 3.5 and 4.0, and above pH 6.0, the enzyme underwent alkaline denaturation. The enzyme was heat labile, and a decrease in activity was found above 55 degrees C. The enzyme activity was inhibited by the addition of urea, cysteine, and pepstatin. No other inhibitor among those tested had any effect. The C. albicans enzyme degraded both the native acid-soluble collagen and the insoluble dentinal collagen.
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Effects of budralazine, a new antihypertensive drug, on regional circulation in various sites of brain and extracranial skeletal muscle and skin in curarized, artificially respirated cats were studied using the thermoelectrical method. Budralazine produced an increase in blood flow in the cerebral cortex and hippocampus. Effects of the drug on blood flow in the hypothalamus and amygdala were inconsistent. Budralazine produced an apparent increase in muscular blood flow, whereas the drug did not consistently alter dermal blood flow. Budralazine produced a mild and sustained fall in blood pressure, particularly after the repeated administration. Thus, the action of budralazine seems to be mainly one of a smooth muscle relaxant effect. The mode of action of the drug seems to differ from that of papaverine or hydralazine.
Among the reported complications of the antifibrinolytic therapy in the treatment of ruptured intracranial aneurysms, nausea and vomiting, cerebral arteriopathy and secondary hydrocephalus would be a matter of concern in its possible CNS involvement. However, little is known about the possibility of direct cerebral effect in synthetic antifibrinolytics. A simply designed animal experiment disclosed remarkable effects on electroencephalography, blood flow of the cerebral cortex and intracranial pressure. Such antifibrinolytics should not be given intrathecally in any situation even if the accumulation of the agents in cerebrospinal fluid is essential to prevent recurrent hemorrhage.
Effects of cinepazide, a vasoactive agent, on regional circulations in various sites of brain and other organs in curarized, artificially respirated cats were studied using a thermoelectrical method. The mechanism of the vascular effect was also investigated. Cinepazide produced a marked increase in blood flow in the cerebellar cortex and an apparent increase in blood flow in the cerebral cortex. Effects of the drug on blood flow in the thalamus, hypothalamus and amygdala were inconsistent. Cinepazide produced the most significant increase in myocardial blood flow and also an apparent increase in muscular blood flow, whereas the drug did not consistently alter hepatic blood flow, and decreased renal and dermal blood flow. Cinepazide produced a mild and sustained fall in blood pressure, however, a transient slight rise in blood pressure was noted when the drug was given into the vertebral artery. It seems possible that the action of cinepazide might involve a mild stimulation of beta adrenergic receptors and slight stimulation of alpha adrenergic receptors but not cholinergic receptors, in the cerebral and peripheral vascular systems. Increase in blood flow induced by cinepazide seems to be mainly due to the smooth muscle relaxant effect and may be mediated via a metabolic mechanism.
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The role of sympathetic nerves in the development of responsiveness of smooth muscle to drugs was investigated using the expansor secondariorum muscle of 2- to 40-day-old chicks. The normal developmental decrease in the responsiveness of the muscle to acetylcholine was prevented by surgical transection of the nerve or chronic treatment with guanethidine, while it was facilitated by chronic treatment with dimethylphenylpiperazinium. Sensitivity of the muscle to noradrenaline, remaining constant during normal development, was increased by nerve section or guanethidine treatment, while it was slightly decreased by dimethylphenylpipe-azinium treatment. These results suggest that sympathetic nerves regulate the development of the responsiveness of the chick expansor secundariorum muscle to drugs, at least the developmental decrease in responsiveness to acetylcholine.
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Effects of ifenprodil on the regional blood flow of some organs (skin, skeletal muscle, liver, myocardium, kidney, cerebral cortex, hippocampus, amygdala, hypothalamus and cerebellar cortex) of the curarized cat under artificial respiration were studied using the thermoelectrical method. 1) Blood flow in the skin decreased, whereas renal blood flow increased. 2) Blood flow in the liver showed a biphasic response, being more active in the increasing phase. 3) Blood flow in the hypothalamus and cerebellar cortex (vertebral arterial region), skeletal muscle and myocardium markedly increased. 4) Blood flow in the cerebral cortex and hippocampus (external carotid arterial region) was not influenced by ifenprodil, but slight changes were noticed and were dependent on the blood pressure response. 5) Blood pressure fell in accordance with the dose level of ifenprodil given i.v. 6) Those results suggest that the mechanisms of action of ifenprodil are alpha-adrenergic blocking, beta-mimetic and direct vasodilating. A cholinergic effect was also suggested. 7) On certain functions such as blood flow in the skin and blood pressure a dual action, that is alpha adreno-mimetic and -lytic was seen. 8) Concerning the vascular smooth muscle relaxative action, it would appear that ifenprodil has not only a direct effect but also a secondary effect resulting presumably from its action on the local metabolism.
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