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S Usuda

Publications and source records attributed to S Usuda.

86 records · Page 5Linked to original sources
PubMed1981

Synthesis and neuroleptic activity of benzamides. Cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds.

Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.

Animals↗
PubMed1979

Pharmacological and biochemical studies on a new potential neuroleptic, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050).

Pharmacological and biochemical properties of a novel compound, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050) were compared with those of haloperidol (HPD) and chlorpromazine (CPZ) in animals. YM-08050 was more potent than either HPD or CPZ in inhibitory effects on a variety of behaviors such as apomorphine-induced stereotypes behavior and emesis, methamphetamine-induced stereotyped behavior, conditioned avoidance response and open field behavior. YM-08050 induced catalepsy only at much higher doses than to exhibit the inhibitory activities. The inhibitory effects of YM-08050 on [3H]dopamine binding and dopamine-sensitive adenylate cyclase in the synaptic membrane fractions of canine caudate nucleus were much greater than those of HPD and CPZ. The results suggest that YM-08050, a potent central dopaminergic blocker, is a potential antipsychotic drug with less extrapyramidal side effects than those of HPD and CPZ.

Animals↗
PubMed1976

Vasodilator profile of a new 1,4-dihydropyridine derivative, 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino)]-ethyl ester 5-methyl ester hydrochloride (YC-93).

A new 1,4-dihydropyridine derivative, 2,6-dimethyl-4-(3-nitrophenyl)-4,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino)]-ethyl ester 5-methyl ester hydrochloride (YC-93), when i.v. injected into anesthetized dogs, exhibited not only a greated vasodilation in both cerebral and coronary than in femoral vessels, but also about 100 to 300 times higher potency as well as longer durability than any of reference drugs such as isoxsupurine, papaverine and cinnarizine. YC-93 was also effective in vasodilation by i.m. and i.d. administration. When administered into vertebral and coronary arteries, YC-93 caused vasodilation at the doses that did not affect systemic blood pressure. YC-93 did not potentiate the vasodilator effect of adenosine, and vasodilation by YC-93 was influenced by neither propranolol, atropine, diphenhydramine nor aminophylline. Acute toxicity (LD50) of YC-93 was almost the same as that of papaverine in mice and rats. Thus, YC-93 is a potent bu low-toxic vasodilator agent acting preferentially and perhaps directly on cerebral and coronary vascular beds and is well absorbed from gastrointestinal tract into blood stream.

Animals↗
PubMedDate not supplied

Antibody to the receptor for polymerized human serum albumin in acute and persistent infection with hepatitis B virus.

The antibody against the receptor for polymerized human serum albumin was determined by radioimmunoassay. The method involved the inhibition by the test serum, absorbed with HBsAg particles without the receptor, on the binding of polymerized human serum albumin to HBsAg particles with the receptor fixed on a solid support. The amount of polymerized human serum albumin captured by the receptor on HBsAg was then determined by the radiolabeled monoclonal antibody directed to an epitope specific for polymerized human serum albumin. In acute infection, the antibody to the receptor for polymerized human serum albumin appeared in the early recovery phase while HBs antigenemia and elevated transaminase levels were still present, preceding the antibody to HBsAg (anti-HBs). The antibody was detected in 4 (1%) of 358 sera from asymptomatic carriers of HBsAg containing antibody to HBeAg, and in none of 67 sera containing HBeAg. Although the antibody was found in as many as 111 (74%) of 150 sera from blood donors who had presumably acquired anti-HBs after natural infection, it was not detected in any sera from 77 recipients of hepatitis B vaccine who had seroconverted for anti-HBs. On the basis of these observations, the determination of antibody to the receptor for polymerized human serum albumin helps in further understanding the immunity to hepatitis B virus.

Acute Disease↗
PubMedDate not supplied

Immunological responses against an autologous human hepatocellular carcinoma cell line.

We performed a detailed analysis of immune responses in a hepatocellular carcinoma (HCC) cell line and effector cells obtained from a patient with HCC. We examined the cytotoxic activity of natural killer (NK) cells, lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) against an autologous tumour cell line (SUHC-1) to investigate the immune mechanism of human lymphocytes against HCC cells. Cytotoxic T lymphocytes were induced by co-culturing of peripheral blood lymphocytes (PBL) and SUHC-1 cells, mixed lymphocyte and tumour cell culture (MLTC). The susceptibility of SUHC-1 to NK and LAK cells was similar to that of other allogeneic cell lines, such as K562, PLC/PRF/5 and Mahlavu. Effector cells induced in the primary MLTC had high cytotoxic activity but were not specific for SUHC-1. Cytotoxic T lymphocytes with specific activity against SUHC-1 were induced after PBL were stimulated five times at 7-10 day intervals with SUHC-1 and low-dose recombinant interleukin-2 (rIL-2), suggesting that as the culture progressed, broadly reactive effector cells disappeared and specific effector cells survived. The specific effector cells were identified as CD3+/CD4+ and CD3+/CD8+ T-lymphocyte subsets. The recognition mechanisms of CD3+/CD4+ CTL remain unresolved because the cytotoxicities were not inhibited by anti-CD4 and anti-major histocompatibility complex (MHC) class II monoclonal antibodies (MoAb). Treatment of cells with anti-CD3, anti-CD8 and anti-MHC class I MoAb partially inhibited lysis. These results demonstrated that the T-cell receptor (TCR)/CD3 complex appeared to be involved in SUHC-1 specific antigen recognition and antigen recognition of CD3+/CD8+ CTL was MHC class I restricted.

Aged↗
PubMedDate not supplied

Type C chronic hepatitis associated with thrombocytopenia in two patients.

Portal hypertension in the presence of chronic hepatitis is generally thought to develop during the progression of the chronic hepatitis to cirrhosis. Before the establishment of assays for diagnosing hepatitis C virus infection, such a case of portal hypertension without liver cirrhosis could be misdiagnosed as idiopathic portal hypertension. It had not fully determined whether portal hypertension might precede the onset of cirrhosis in type C chronic hepatitis. This report presents two cases of women with chronic hepatitis C who developed severe thrombocytopenia; each showed splenomegaly and hypersplenism due to portal hypertension. Angiographic study and histological analysis were conducted to determine the cause of the portal hypertension. Histological evaluation showed an intrahepatic presinusoidal block pattern and fibrotic changes in the periportal area, but no evidence of liver cirrhosis or of other incidental complications such as idiopathic portal hypertension. Both of these patients exhibited normal platelet counts after splenectomy. Thus, type C chronic hepatitis can lead to portal hypertension, as demonstrated in these two patients.

Chronic Disease↗