Katsumi Hirose

Differential effects of sulpiride and metoclopramide on brain

SummarySulpiride (SUL) is more efficacious in antipsychotic activity than metoclopramide (MET), although both appear to possess almost equal affinities for dopamine (DA) receptors. We studied the effects of SUL and MET on the brain homovanillic acid (HVA) level and shuttle box avoidance to clarify their differential modes of action on the blockade of DA receptors. SUL was several times less potent than MET, which was about 50 times less potent than the control drug haloperidol (HAL), for increasing HVA at 4 h after s.c. administration. However, SUL was about 50 times more potent than MET and about equipotent to HAL, at 2 h after drug administration into the lateral ventricle. The potency of SUL by intraventricular administration was 20-fold or more than that by intracisternal administration. HAL and MET did not show such a discrepancy. The HVA level reached the maximum 1 h after intraventricular administration of MET or HAL, while s.c., intracisternal or intraventricular administration of SUL caused a gradual increase in the HVA level with the maximum being reached after 6–8 h. In shuttle box avoidance, MET was about 25 times more potent than SUL by intraperitoneal administration but about 200 times less potent than SUL, which was about 10 times more potent than HAL, by intraventricular administration. These results suggest that SUL causes a potent, long-lasting blockade of DA receptors, while MET has only a weak, short-lasting action. These findings may be related to the differences in their clinical efficacy.

Time course analyses of kinins and other mediators in plasma exudation of rat kaolin-induced pleurisy

Pleurisy was induced in rats by an intrapleural injection of 0.5 ml of 1% kaolin. The exudation of plasma into the pleural cavity showed two peaks at 20 min and 3-5 h after the kaolin injection. The volume of the pleural fluid increased gradually up to 5 h. The effects of treatment with mepyramine, methysergide, captopril, bromelain and indomethacin suggested that the early phase (20 min) of exudation was mediated mainly by kinins, histamine and 5-HT, and that the late phase (3 h) was mediated by prostaglandins (PGs) and possibly kinins. We measured the levels of histamine, kinin and PG in the pleural exudate to verify the involvement of the mediators mentioned above. Intracellular histamine levels decreased markedly and extracellular histamine levels increased significantly 20 min after the induction of kaolin pleurisy. Only threshold levels of kinin were detected after the induction of pleurisy. Captopril treatment, however, increased kinin levels which peaked at 20 min and decreased rapidly thereafter. Levels of 6-keto-PGF1 alpha and thromboxane B2 showed a peak at 20 min, whereas levels of PGE2 increased gradually from 20 min to 5 h. These results indicate that kaolin-induced pleurisy is a kinin-related inflammation and could be used as a model for studying the in vivo interaction of the kallikrein-kinin system and PGs at inflammatory sites.

Partition of pyridine bases between benzene and aqueous solution

Abstract The partition of pyridine bases between benzene and 0.10 M (Na, H)ClO4 aqueous solution has been studied at 25°C, total concentration of the pyridine base being less than 5 × 10−2 M. The pyridine bases used include pyridine, 2-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine, 3,5-dimethylpyridine and 2,4,6-trimethylpyridine. The hydrated and unhydrated pyridine bases are both present in the organic and aqueous phases. After an appropriate correction for hydration, the partition of pyridines is consistent with the regular solution theory.

Synergistic extraction of copper(II) with capric acid in the presence of pyridine

Abstract Synergistic extraction of zinc(II) with capric acid in the presence of pyridine was carried out at 25°C and at an aqueous ionic strength of 0.1 mol dm−3 (NaClO4), the total concentration of zinc, that of capric acid and that of pyridine being less than 4 × 10−3 mol dm−3, 0.15–1.5 mol dm−3 and 1.32 × 10−2 mol dm−3 respectively. The synergistic effect is interpreted by the formation of the following mixed ligand complexes in benzene: ZnA2(HA)B and ZnA2(HA)3B. The extraction equilibria are described as follows: Zn 2+ + B w + 1.5( HA ) 2,o ( ZnA 2+ (HA)B ) w + 2 H − Zn 2+ + B w + 2.5( HA ) 2,o ( ZnA 2+ (HA) 3+ B ) o + 2 H − with log Kex(111) = − 7.02 ± 0.10 and log Kex(113) = − 6.09 ± 0.05.

Extraction of uranium(VI) with capric acid

Abstract Partition of uranium(VI) was carried out at 25°C between water and benzene containing capric acid in excess, total concentration of uranium(VI) and that of capric acid being less than 3 × 10−3 M and 0·10–1·50 M, respectively. Under the experimental conditions there exist two monomeric uranyl caprates with different compositions in the organic phase: UO2R22HR and UO2R24HR. Thus the extraction equilibria for uranium(VI) are described as follows: with the following extraction constants: log K 12 = log ([UO 2 R 2 2HR] 0 [H + ] 2 [UO 2 2+ ] −1 [(HR) 2 ] 0 −2 ) = −5·66±0·05 log K 12 = log ([UO 2 R 2 2HR] 0 [H + ] 2 [UO 2 2+ ] −1 [(HR) 2 ] 0 −3 ) = −5·83±0·15 The equilibrium for the uranyl caprates in the organic phase can be formulated as: where log K ƒ = −0·17 ± 0·10 .