Biomedical subjects

C Nakagawa

Publications and source records attributed to C Nakagawa.

52 records · Page 3Linked to original sources

PubMed1988

Veno-occlusive disease of the liver in a patient with allergic granulomatous angiitis.

A 45-yr-old woman, with asthma and skin erythema, was diagnosed as having allergic granulomatous angiitis. Leukocytosis accompanied by hypereosinophilia and characteristic histological findings of skin lesions also were present. Upon laparoscopy and liver biopsy, the liver showed a congestive appearance and, histologically, showed thickening of the central vein walls, as well as narrowing of the lumens with collagenous fibers, and pericentral hemorrhage with hepatocyte degeneration. A diagnosis of veno-occlusive disease of the liver was made. This is the first report on a case of veno-occlusive disease of the liver occurring in association with allergic granulomatous angiitis.

Female↗

PubMed1987

Further studies on (+/-)-YM-12617, a potent and selective alpha 1-adrenoceptor antagonist and its individual optical enantiomers.

YM-12617, 5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2-methoxybenzenesulfonamide HCl is structurally novel, an extremely potent and highly selective alpha 1-adrenoceptor antagonist. An asymmetric center exists at the alpha-carbon atom in the phenethylamine portion of YM-12617, therefore two optical enantiomers exist. alpha-Adrenoceptor blocking properties and hypotensive activities of YM-12617 and its enantiomers have been compared in vitro and in vivo. 1. In the isolated rabbit aorta, R(-)- and S(+)-YM-12617 competitively antagonized phenylephrine-induced contraction with pA2 values of 9.95 and 7.69, respectively. Although R(-)- and S(+)-YM-12617 were also competitive antagonists toward UK-14,304 at prejunctional alpha 2-adrenoceptors in the isolated guinea-pig ileum, the affinities of R(-)-YM-12617 (pA2 = 6.18) and S(+)-YM-12617 (pA2 = 5.64) for these receptors were 5,900 and 110 times lower than those displayed for postjunctional alpha 1-adrenoceptors in the isolated rabbit aorta. 2. R(-)- and S(+)-YM-12617 displaced both 3H-prazosin and 3H-idazoxan binding to rat brain membranes; however, the affinities of the R(-)- and S(+)-enantiomers for alpha 1-adrenoceptors (pKi = 9.95 and 7.83, respectively) were 21,000 and 72 times higher than those for alpha 2-adrenoceptors (pKi = 5.62 and 5.97), respectively. 3. Based on pA2 values obtained in the isolated tissues and pKi values in the binding assays, R(-)-YM-12617 was 132-182 times more potent than S(+)-YM-12617 as an antagonist at alpha 1-adrenoceptors. In contrast, the R(-)- and S(+)-enantiomers were similar in potency at blocking alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1987

Selectivity and specificity for alpha 1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats.

The selectivity and specificity for alpha 1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg-1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg-1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an alpha 1-adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in-vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective alpha 1-adrenoceptor blocking activity and its activity was specific for alpha 1-adrenoceptors.

Administration, Oral↗

PubMed1987

In vitro characterization of alpha-adrenergic receptor in rabbit detrusor muscle.

In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2 alpha, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine greater than PGF2 alpha greater than histamine greater than methoxamine. Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN-A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2-pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10(-5) M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-)- and S(+)-YM-12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively antagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by alpha 1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by alpha 1-adrenergic receptor agonist is smaller than those stimulated by the other receptor agonists.

Adrenergic alpha-Agonists↗

PubMed1987

[A case of hepatocellular carcinoma with extrahepatic portal vein obstruction due to tumor invasion, responsive to oral administration of UFT].

A 38-year-old male was admitted to Ikeda Municipal Hospital because of thrombocytopenic purpura and abnormal liver function. Computed tomography and ultrasonography of the liver showed a 5 by 5 cm mass in the right lobe of the liver. Hepatic angiography revealed a hypervascular tumor in the right lobe of the liver and extrahepatic portal venous obstruction. A diagnosis of hepatocellular carcinoma with extrahepatic portal venous obstruction due to tumor invasion was made. Endoscopic examination showed marked esophageal varices with red color sign. Oral administration of UFT at a daily dose of 400 mg was started. Though ascites and frequent hemorrhage from esophageal varices were observed, these symptoms disappeared completely after 8 months administration of UFT. Endoscopic examination revealed disappearance of the esophageal varices, and recanalization of the extrahepatic portal vein was confirmed by the second hepatic angiography. Computed tomography showed no growth of the liver tumor. These data suggest that UFT was effective in this case.

Administration, Oral↗

PubMed1986

Adrenoceptor blocking and cardiovascular effects of the optical isomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent, and the corresponding desoxy derivative (YM-11133) in rats.

The pharmacological activities of the enantiomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor antagonist, and the corresponding desoxy derivative (YM-11133) were investigated in the cardiovascular system of rats. The optical isomers of amosulalol and YM-11133 antagonized the vasopressor effect of phenylephrine and the positive chronotropic effect of isoproterenol in normotensive pithed rats. Based on DR2 values (micrograms/kg, i.v.) obtained from Schild plots, (+)-amosulalol and YM-11133 (DR2 = 30) were approximately 10 times more potent than (-)-amosulalol (DR2 = 324) in blocking alpha 1-adrenoceptors. For beta 1-adrenoceptors, in contrast, (-)-amosulalol (DR2 = 107) was approximately 60 times more potent than (+)-amosulalol (DR2 = 6460), which was almost equipotent with YM-11133 (DR2 = 3250). The results indicate that the optical isomers of amosulalol interact differently with alpha 1- and beta 1-adrenoceptors. The effects of these phenethylamines on blood pressure and heart rate were studied in urethane-anesthetized rats (i.v.). The rank order of hypotensive potency in anesthetized rats [+)- = desoxy greater than (-)-form) was consistent with the rank order of alpha 1-adrenoceptor antagonism in pithed rats. In contrast, (-)-amosulalol having a more potent beta 1-adrenoceptor antagonist activity than (+)-amosulalol and YM-11133 only produced dose-dependent bradycardia at the hypotensive doses. The results indicate that the vascular alpha 1- and cardiac beta 1-adrenoceptor blocking activities of the optical isomers of amosulalol contribute to their hypotensive and bradycardia, respectively. Thus, the racemate of amosulalol appears to exert an overall activity reflecting the activities of the individual isomers.

Adrenergic alpha-Antagonists↗

PubMed1986

[Combination chemotherapy of cisplatin, vincristine and peplomycin for patients with head and neck carcinoma].

The effectiveness of combined CDDP chemotherapy with other anticancer drugs in patients with head and neck carcinoma was investigated. The response rate for COP therapy (CDDP, Vincristine, Peplomycin) was better than those for CDDP administration only or CP (CDDP Peplomycin) therapy for carcinomas of the head and neck. Forty-seven cases treated with COP therapy, were analyzed in detail. (1) Non-treated fresh cases showed a better response than recurrent cases. In other words, the induction chemotherapy is useful. (2) The grade of differentiation of squamous cell carcinoma had no correlation with the response. (3) No relationship between the primary site and the respose rate was detected. (4) Nephrotoxicity was considered to be the dose-limiting factor of CDDP therapy. COP therapy did not show any remarkable side effects. COP chemotherapy is therefore concluded to be effective for the treatment of squamous cell carcinomas of the head and neck.

Adult↗

PubMed1986

Alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 in rabbit lower urinary tract and prostate.

The alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 (5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2-methoxybenzenesulfonamide HCl), a potent and selective alpha-1 adrenoceptor antagonist, were evaluated in the rabbit lower urinary tract and prostate. R-(-)-YM-12617 (1 X 10(-10) to 3 X 10(-9) M) and S-(+)-YM-12617 (3 X 10(-8) to 3 X 10(-7) M) antagonized phenylephrine-induced contraction in a competitive manner in the urinary bladder base (trigone), proximal urethra and prostate. The mean pA2 value for R-(-)-YM-12617 at the alpha-1 adrenoceptor of trigone, urethra and prostate was 9.91, 9.62 and 9.92, respectively, and that for S-(+)-YM-12617 was 8.09, 7.92 and 7.77, respectively. Therefore, R-(-)-YM-12617 is a 50 to 141 times more potent antagonist than S-(+)-YM-12617 at the alpha-1 adrenoceptor in these tissues. The present results also indicate that the alpha-1 adrenoceptor in the lower urinary tract and prostate can distinguish clearly between the optical isomers of YM-12617. Similar results were obtained in the aorta of rabbits in which a dramatic stereochemical preference of R-(-)-YM-12617 for the alpha-1 adrenoceptor also exists.

Adrenergic alpha-Antagonists↗

PubMed1985

Autonomic and antihypertensive activity of oral amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent in conscious rats.

The autonomic and antihypertensive activities of amosulalol (YM-09538) were studied in conscious rats. Single oral administration of amosulalol antagonized the phenylephrine-induced pressor and isoproterenol-induced positive chronotropic responses with DR10 values of 11.5 and 13.6 mg/kg in pithed rats, respectively, indicating that the compound inhibits both alpha 1- and beta 1-adrenoceptors to almost the same extent in agreement with previously reported results in vitro. Amosulalol was approximately 50 times less potent than prazosin and 12 times more potent than labetalol at alpha 1-adrenoceptors, and it was approximately as effective as labetalol and 2 times more potent than propranolol at beta 1-adrenoceptors. In spontaneously hypertensive rats (SHR), renal hypertensive rats and DOCA/salt hypertensive rats, a single oral administration of amosulalol (3-30 mg/kg) lowered acutely systolic blood pressure with a duration of over 6 hr and was found to be approximately 50 times less potent than prazosin and 3 times more potent than labetalol in lowering blood pressure. Propranolol did not cause such an immediate hypotensive effect. Amosulalol and labetalol did not increase heart rate, whereas prazosin induced a tachycardia in the hypertensive rats. Repeated oral administrations of amosulalol and labetalol (50 mg/kg/day, b.i.d., for 12 weeks) produced not only an antihypertensive effect without evidence of tolerance, but also reductions in plasma renin activity (PRA) and heart rate in SHR with established hypertension. We conclude that alpha-adrenoceptor blockade by amosulalol might account for its antihypertensive activity and that its beta-adrenoceptor blockade might inhibit reflexogenic increases in heart rate and PRA due to the reduction in blood pressure.

Adrenergic alpha-Antagonists↗

PubMed1984