TACHYPHYLAXIS OF INDIRECTLY ACTING SYMPATHOMIMETIC AMINES:III INFLUENCE OF ACUTELY AND CHRONICALLY ADMINISTERED RESERPINE
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概要
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Observations were made of influence of acute and chronic reserpinization upon the pressor effects of intravenously administered ephedrine-like (Ephlike) drugs and on tachyphylaxis arising from repeated dosage of these drugs in atropinized dogs under morphine-pentobarbital anesthesia. 1) In acutely reserpinized dogs, repeated administration of ephedrine (Eph), methamphetamine (Met), Pheniprazine (Ph) and tyramine (Ty) at dosage level of 0.5 mg/kg caused pressor effects more prominent consistently and slightly than in unreserpinized ones. With Eph, Met and Ty administered repeatedly in doses of 1 mg/kg, diminution of the pressor response was noted to be more slightly marked in the dogs given reserpine (Res) than that in the unreserpinized controls ; hence a slight enhancement of tachyphylaxis to these drugs by acute reserpinization. With Ph, in contrast, marked pressor effects occurred repeatedly and the tachyphylactic tendency was accordingly allayed to a considerable extent. If Res was intitially injected the tachyphylactic response to Eph, Met and Ty was somewhat profound in an occasional case, yet the development of tachyphylaxis was not significantly hastened by the administration of Res. 2) In animals with tachyphylactic response to repeated Eph, Met or Ph dosage with the consequent disappearance of pressor effects, reserpinization gave rise to a persistent elevation in blood pressure even after the appearance of hypotension (reversal effect). Res, however, failed to bring about any conspicuous rise in blood pressure when it was injected after disappearance of the pressor response following repeated high dosage of Ty. After reserpinization no alterations in the pattern of blood pressure lowering response (reversal effect) were noted to occur with Eph, Met and Ph, whereas with Ty, a slight recovery to pressor effects occurred. 3) A tendency was noted to exsist for the cross tachyphylaxis with these Eph-like drugs to be some what conspicuously provoked by the administration of Res. Especially, the pressor effect of Ty was observed to be somewhat markedly diminished with an augmentation of tachyphylaxis in animals having been received Res plus Eph or Met. 4) In chronically reserpinized dogs, the pressor response to Eph-like drugs was remarkably modest from the beginnig and further gradually diminished, yet never subsided, as the drugs were injected repeatedly. These results obtained indicate that acute or chronic reserpinization may in some instances slightly enhance the tachyphylactic tendency to Eph-like drugs, but cause no particularly rapid disappearance of pressor effect, and that the norepinephrine (Nor) depletion by Res and the development of tachyphylaxis to these drugs have not particularly intimate relation to each other. Furthermore, the mechanism of actions of Eph-like agents was also discussed.
- 久留米大学医学部 The Kurume Medical Journal 編集部の論文
著者
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Yamamoto Ryuichi
Department Of Internal Medicine Japan Self Defense Forces Fukuoka Hospital
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Takasaki Koichiro
Department Of Pharmacology Miyazaki Medical College
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URABE MASANOBU
Department of Pharmacology, Daiichi College of Pharmaceutical Sciences
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URABE MASANOBU
Department of Pharmacology, Daiichi College of Pharmaceutical SciencesFukuoka
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