Amino-oxy Acetic Acid(AOAA)の薬理作用

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Pharmacological properties of amino-oxyacetic acid (AOAA), an inhibitor of γ-aminobutyric acid-α-ketoglutaric acid (GABA-AKG) transaminase, were examined with following results. 1. The acute intraperitoneal LD50 for AOAA were 286mg/kg in mice and 135mg/kg in rats. Behavioral changes seen following administration of AOAA were a decrease in spontaneous movements and a gradual sedation in all species tested. Vomiting was observed in cats, dogs and monkeys. In large doses, the clonic convulsion that seemed to be antagonized with pentobarbital was induced in various species of animal. 2. On the chronic toxicity test of rats (0.1-20mg/kg/day intraperitoneally for six months), the maximum tolerated daily dose was about 1mg/kg. This dose caused loss of weight, but did not kill any animal. The dose of 5mg/kg/day had no remarkable effects on blood pictures. Histopathological examination revealed pulmonary emphysema attributable to drug action. 3. The rabbit rectal temperature was lowered after subcutaneous or intravenous injection of AOAA (5-50 mg/kg) . 4. AOAA administered intravenously (10-120mg/kg) to pentobarbitalized dogs produced regularly a transitory depressor response accompanied with a marked respiratory excitation. This hypotensive effect was not reduced or abolished with following drugs: atropine, diphenhydramine, procain and papaverine given at pharmacologically active dose levels. Moreover, the deprssor action had remained during the pretreatment with the ganglionic blocking agents. AOAA did not modify the pressor response in blood pressure to occlusion of both carotid arteries, and its depressor action was not decreased with severance of bilateral cervical nerves, vagi, sympathetics and depressor nerves combined with carotid sinuses denervation. Depressor action of intra internal carotid arterial injection of AOAA was approximately ten times as potent as that of intravenous injection. Cardiac function was reduced both in the isolated rabbit heart and in the dog heart-lung preparation. AOAA showed the peripheral vasoconstriction in the rabbit ear vesseles and in the dog cross perfused hind quarter. 5. AOAA reduced both the tone and the amplitude of the spontaneously contracting rabbit ileum, while AOAA produced oxytocic action in the isolated rat uterus. 6. AOAA potentiated the responses both to direct and indirect stimulation in the isolated rat phrenic nerve-diaphragm preparation in large doses, and in very large doses reduced the responses both to direct and to indirect stimulation. Though positive effects were obtained, the concentrations used would be unlikely to be achieved in vivo and thus discontinued the experiments.
学校法人昭和大学・昭和医学会の論文

Amino-oxy Acetic Acid(AOAA)の薬理作用

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