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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 1,189 records · Page 66Linked to original sources
PubMed1979

Metabolites of loperamide in rats.

Following intraperitoneal administration to rats of [14C]loperamide, [carbonyl-14] 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-alpha, alpha-diphenyl-1-piperidine butyramide, metabolites in feces and urine were separated, and identified by means of mass spectrometry. In feces, six metabolites were identified in addition to the unchanged drug. The main metabolic pathways involved are dealkylation in the dimethyl amide moiety to give desmethyl- and didesmethylloperamide, both of which were in turn monohydroxylated either in the alpha-phenyl ring or possibly in the alpha-carbon in the piperidine ring. It is noteworthy that metabolites hydroxylated in the piperidine ring were isolated as pyridinium derivatives, possibly due to spontaneous aromatization of its 2,4-dihydroxy-4-(p-chlorophenyl)piperidine ring. In urine, only two metabolites were found and identified to be desmethyl- and didesmethylloperamide, since [14C]loperamide was excreted into urine only in a small amount.

Animals↗
PubMed1979

Disposition and metabolism of [14C]loperamide in rats.

Following oral administration of [14C]loperamide hydrochloride in 1 mg/kg to rats, plasma levels of radioactivity reached maximum at 4 hrs and decreased with a half-life of 4.1 hrs. Radioactivity in 96-hr feces accounted for 95% of the dose, with 30% associated with unchanged drug, while that in urine only 3.5%. Radioactivity in 48-hr bile accounted for 42% of the dose associated entirely with metabolites. 3% of the dose was found at the level of the enterohepatic cycles. These findings show that about 70% of the dose with absorbed by intestine, the target tissue of the drug, a portion (30%) of which was excreted back into intestinal cavity after demethylation, while the remaining 40% transferred to liver by which it was extracted mostly, metabolized extensively and excreted largely into bile, as supported by in vitro demethylating activity in gut segments but none in gut contents, and by in situ marked hepatic extraction of the drug. Main metabolic pathways involved are described.

Animals↗
PubMed1979

Effects of periodic saccades on the body sway in human subjects.

The body sway in upright standing was decreased by periodic saccades. The decrease was also observed during voluntary rapid eye movements in complete darkness, indicating that the visual information was not concerned with the decrease of the sway. Continuous eye rotations did not affect the body sway, showing that the repetitive activation of eye muscle proprioceptors was not the cause of the sway reduction. These results suggest that some information related to the execution of saccades may affect the spinal motor system and cause the stabilization of the standing posture.

Adult↗
PubMed1979

Role of brain amines in the fetal hyperpyrexia caused by tranylcypromine in LiCl-pretreated rats.

Tranylcypromine (TCP), a monoamine oxidase inhibitor, caused a fatal hyperpyrexia in rats pretreated with LiCl once a day for 4 days. Pretreatment with LiCl alone did not alter the level of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) in the brain. In fatal hyperpyrexia caused by LiCl plus TCP, the brain 5-HT and DA levels were increased, whereas the brain NE level was decreased. Reserpine and alpha-methyl-p-tyrosine completely prevented the hyperpyrexia, but FLA-63 did not show any effect. The hyperpyrexia was completely prevented by p-chlorophenylalanine (PCPA) given 72 hours before TCP but not by PCPA given 24 hours before TCP. Haloperidol and chlorpromazine, DA receptor blockers, inhibited the fatal hyperpyrexia, while cyproheptadine and methysergide, 5-HT receptor blockers, did not. These results suggest that DA plays an essential role in the hyperpyrexia induced by the combination of TCP and LiCl in rats, but the involvement of 5-HT is inconclusive.

Amines↗
PubMed1979

Amines and the rat exocrine pancreas: (1). Effects of receptor blockers on turnover of L-dopa.

The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA-blockers (haloperidol, sulpiride, and pimozide) and alpha-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, beta-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion. Because DA- and alpha-blockers produced an increase in the accumulation of DA, dopaminergic and/or alpha-adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.

Adrenergic alpha-Antagonists↗
PubMed1979

Amines and the rat exocrine pancreas: (2) Effects of receptor blockers on turnover of L-5HTP.

The metabolism of L-5HTP by the rat exocrine pancreas, and effects of blockers on the metabolism were studied by fluorescent histochemical and chemical methods. Histochemically, 5-hydroxytryptamine (5-HT) blockers (methyserigide and cyprohepatdine) and dopamine (DA) blockers (haloperidol and sulpiride) produced no apparent changes in fluorescence pictures after injection of L-5HTP. alpha-blockers (phenoxybenzamine and phentolamine) and monoamine oxidase (MAO) inhibitor (iproniazide) produced an increased accumulation of 5-HT fluorescence in the apical regions of acinar cells where the zymogen granules are stored. Chemically, the 5-HT blockers decreased the 5-HT content after injection of L-5HPT. Sulpiride had no effect. Haloperidol decreased the 5-HT content. MAO inhibitor resulted in a vast accumulation of L-dopa: e.g. (1) L-5HTP was more slowly eliminated, and (2) 5-HT blockers produced a decreased content of 5-HT after injection of L-5HTP, in contrast to the finding that DA-blockers produced an incresed content of DA after injection of L-dopa. The mechanism responsible for the differences is discussed in relation to the possible pharmacological effects of L-5HTP and L-dopa on the secretion from the exocrine pancreas of rats.

5-Hydroxytryptophan↗
PubMed1979

Glycolipids in human lung carcinoma of histologically different types.

Glycolipids were isolated from primary human lung carcinoma tissue of various histologic types: adenocarcinoma, squamous cell carcinoma, and undifferentiated small cell carcinoma. Each type of carcinoma had a characteristic glycolipid pattern. The major glycolipids isolated were ceramide monohexosides, ceramide dihexosides, ceramide trihexosides, globoside, and hematoside. Squamous cell carcinoma and undifferentiated small cell carcinoma showed marked increases of ceramide monohexosides and dihexosides. Adenocarcinoma had a much higher level of the sulfatide (ceramide 3-sulfate-galactoside) as compared to squamous cell carcinoma, undifferentiated small cell carcinoma, or normal lung tissue. Embryonic tissue had more significant levels of sulfatide than did the other carcinomas. Adenocarcinoma had significantly lower levels of glycolipids due mainly to a decrease in the amount of ceramide monohexosides and dihexosides and hematoside.

Adenocarcinoma↗
PubMed1979

Effects of intraventricular and intraspinal 6-hydroxydopamine on blood pressure of DOCA-saline hypertensive rats.

The effects of intraventricular and intraspinal administration of 6-hydroxydopamine (6-OH-DA) on the development and maintenance of DOCA-saline hypertension in rats have been investigated. Intraventricular administration of 6-OH-DA prevented the development of DOCA-saline hypertension in rats, but was ineffective in developed DOCA-saline hypertension. Treatment with intraventricular 6-OH-DA on rise in blood pressure was not secondary to a reduction in salt intake, however, since vehicle-treated rats given a similar reduced salt intake became fully hypertensive. The development of DOCA-saline hypertension was unaffected by pretreatment with intraspinal administration of 6-OH-DA, which produced a virtually complete loss of noradrenaline only in the spinal cord. It is suggested that brain adrenergic neurones may participate in the production of DOCA-saline hypertension but the noradrenergic projections in the spinal cords are not essential for this process.

Animals↗
PubMed1978

Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography.

A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. DU-717 is first extracted with ethyl acetate and, after a clean-up procedure, derivatized with peracetic acid followed by diazomethane to form 2-methyl DU-717 N-oxide (direct methylation leads to mixtures). The N-oxide is then pyrolyzed to 2-methyl DU-717 on a gas chromatograph equipped with electron-capture detection. Accurate determinations are possible over a concentration range from 10 to 150 ng/ml of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/ml. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined.

Administration, Oral↗
PubMed1978

Determination of 1,2-benzisoxazole-3-acetamidoxime hydrochloride (PE-257) in plasma using electron-capture gas chromatography.

A gas chromatographic method has been developed that permits the accurate and specific determination of a new psychotropic agent, PF-257, in plasma. PF-257 is extracted with ethyl acetate from alkaline plasma and, after a clean-up procedure, derivatized with heptafluorobutyric anhydride to form 3-[(5-n-heptafluoropropyl-1,2, 4-oxadiazol-3-yl)methyl]-1,2-benzisoxazole (HOMB). The HOMB is assayed on a gas chromatograph equipped with an electron-capture detector. Accurate determinations of PF-257 are possible in the concentration range from 1-40 ng/ml with a relative standard deviation of 6.8%. The minimum detectable concentration in plasma is 0.1 ng/ml. Plasma levels of PF-257 in rats receiving intravenous or oral dosing (10 mg/kg) were determined.

Animals↗